Perchloroethylene (PCE), a widely used solvent, is classified as a probable human carcinogen. We have studied its genotoxicity, clastogenicity, and cytotoxicity in cultured human peripheral lymphocytes (HPLs). Cytogenetic tests used were the chromosomal aberration (CA), sister chromatid exchange (SCE), mitotic index (MI), replication index (RI), and micronucleus (MN) assays. Positive results were obtained with each of these assays: a dose-dependent increase in CA, a significant increase in SCE, a significant decrease in MI and RI, and an increase in MN frequency at the highest concentration of PCE. These results demonstrate that PCE induces significant genotoxic and clastogenic effects in human peripheral lymphocytes.

As a commonly used material that contacts food, polyethylene glycol terephthalate (PET) may interact with food, and since certain components can migrate, this has become a food safety concern. This study aims to investigate the genotoxicity of PET acetic acid migration solution and its toxic mode of action using an in vivo multi-endpoint genotoxicity evaluation system and quantitative liver proteomics analysis. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups: the PET acetic acid migration solution group, the acetic acid group, the phosphate-buffered saline (PBS) control group, the N-ethyl-N-nitrosourea (ENU) positive control group, and their corresponding satellite groups. PBS and ENU were administered by gavage, while the PET acetic acid migration solution and acetic acid were administered orally in the drinking water. The exposure duration was 35 days, followed by a recovery period of 15 days. The PET acetic acid migration solution can cause heart, liver, and kidney injury in rats. On the 15th day, mutations were seen in the Pig-a gene test. On the 35th day, DNA damage was observed in peripheral blood and liver cells. Gene ontology (GO) analysis of the liver proteomics revealed enrichment in DNA metabolism and binding processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the DNA replication pathway. Immunohistochemical analysis demonstrated a significant increase in 8-hydroxydeoxyguanosine (8-OHdG) and a decrease in single-stranded-binding (SSB) protein in the PET acetic acid migration solution group. In summary, the PET acetic acid migration solution has the potential to induce DNA damage, possibly by inhibiting DNA replication and DNA repair pathways. However, the likelihood of genetic toxicity is low.

Oxidative stress is a major factor for aging. Nicotinamide mononucleotide (NMN) is a naturally occurring bioactive nucleotide and a precursor for nicotinamide adenine dinucleotide (NAD), and accumulating evidences have shown that NMN is a promising anti-aging agent, however, the underlying molecular mechanisms remain to be elucidated. Therefore, in the current study, the protective effects of NMN on oxidative stress-induced damage to cells, in particular, the various types of cell death induced by oxidative stress, were evaluated. It was found that NMN inhibited hydrogen peroxide (HO)-induced decrease in A549 cell viability·HO-triggered reactive oxygen species (ROS) production was also diminished by NMN. Furthermore, results from 8-hydoxy 2 deoxyguanosine (8-OHdG) level, alkaline comet assay, and γ-H2AX foci formation indicated that NMN protected cells from HO-induced DNA damage. Detailed cell death analysis revealed that HO caused A549 cell death mainly through apoptosis and ferroptosis, but not necroptosis or parthanatos, and NMN could effectively inhibit the apoptosis and ferroptosis pathways, thus protected cells from HO-induced cell death. Finally, we validated NMN protected against HO-induced organismal senescence in C. elegans. Taken together, these results suggests that NMN is a potent agent against oxidative stress, which could contribute to its anti-aging effects.

Protoporphyrinogen-oxidase inhibitors (PPOi) are a class of herbicides that target chlorophyll synthesis in plants. Similarly, they affect heme synthesis in mammals, resulting in anemia. A new PPOi development candidate showed micronucleus formation in the bone marrow of rodents in vivo. Increased erythropoiesis has previously been described to increase micronucleus formation in the bone marrow. Hence, the micronuclei (MN) observed after administration of the new PPOi candidate may be caused by increased erythropoiesis rather than direct genotoxicity. To investigate this, the mutagenicity in vitro was examined and found to be clearly negative. In addition, micronucleus formation in vivo was investigated after administration of the new PPOi in doses that caused anemia. Both, erythropoietic and non-erythropoietic tissues, bone marrow and liver, were investigated. Moreover, genotoxicity was investigated by the Comet-assay in erythroid and non-erythroid cells of the bone marrow. The new PPOi did not show mutagenic effects in vitro. The new PPOi induced an increase in the micronucleus counts in the bone marrow of rats, whereas the hepatocytes were not affected. In another study in mice, micronucleus formation was observed in the new PPOi-exposed bone marrow. In parallel, bone marrow cells of the same animals were separated into subpopulations isolating erythroid (selected via their Ter119 surface marker) and non-erythroid (selected by their CD45 surface marker) cells, which were then assessed in a comet assay. Results showed a dose dependent increase in micronucleus frequencies while, increases in % DNA tail intensities in the comet assay were only observed in the erythroid Ter119 subpopulation, but not in non-erythroid bone marrow cells. This provides evidence that the new PPOi induces MN only upon induction of anemia, and that the DNA-damage is only occurring in erythroid cells. The increased micronucleus-formation of the new PPOi in vivo is hence most likely caused by erythropoiesis and not by direct genotoxic actions.

Cockayne Syndrome (CS), a progeroid disorder characterised by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a key component of the transcription-coupled nucleotide excision repair pathway. This study investigates the role of CSB in managing oxidative DNA damage and preserving telomere integrity under oxidative stress. Using CSB-deficient human fibroblasts (CS-B) and matched controls, we exposed cells to acute and chronic oxidative stress via hydrogen peroxide (H₂O₂) and elevated oxygen (40 %) levels. CS-B fibroblasts showed relative resistance to acute oxidative stress in terms of cell death, maintaining viability and displaying limited cell cycle arrest. In contrast, chronic oxidative exposure induced accelerated senescence in CS-B cells, evidenced by increased telomere attrition, senescent morphology, and early activation of senescence-associated β-galactosidase associated with increased DNA damage and aberrant DNA repair. Gene expression profiling revealed downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts following H₂O₂ treatment, indicating impaired damage response pathways. These findings highlight the essential role of CSB in genome maintenance and suggest that its loss contributes to CS pathology through heightened sensitivity to chronic oxidative stress and telomere dysfunction. This work enhances our understanding of CS-related cellular mechanisms and may inform future therapeutic strategies targeting oxidative stress and DNA repair.

Asthma is a chronic, non-communicable respiratory disorder affecting approximately 262 million people worldwide, with India projected to become one of the leading countries in prevalence. Asthma is well-established as a condition of chronic inflammation of the airways and related to systemic oxidative stress, but relatively not much is known about the genomic instability associated with asthma. On the other hand, obesity is found in 650 million people worldwide and 113 million people in India. Studies reported links between asthma and obesity, which include adipose tissue dysfunction and inefficient blood monocyte efferocytosis. Obesity enhances reactive oxygen species (ROS) production and inflammation, leading to DNA lesions. Thus, the aim of this study was to assess the DNA damage and frequencies of micronuclei (MNi), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in the lymphocytes of asthma patients and obese individuals. This study evaluates the DNA damage and nuclear anomalies in (n = 435) subjects (asthma patients n = 100, asthmatic obese patients n = 131, obese n = 100 and controls n = 104). An alkaline comet assay was used to assess DNA damage and nuclear anomalies were assessed by cytokinesis block micronucleus cytome (CBMN-Cyt) assay. All subjects were recruited between the age of 20 and 60 years. The total DNA damage, MNi, and frequency of total nuclear anomalies were found to be significantly higher in asthma male and female patients, asthmatic obese male and female patients, and obese males and females in comparison to control males and females (p < 0.05). The total comet score showed a positive correlation with the frequency of total nuclear anomalies in asthma male and female patients and obese males, respectively. Overall the findings demonstrate that inflammation and oxidative stress in asthma and obesity lead to DNA damage and genomic instability.

Computed tomography (CT) is a widely used diagnostic imaging modality that contributes significantly to human healthcare. Despite the advantage, its extensive use increased concerns due to receiving radiation doses to pediatric patient's over adults during CT imaging. We evaluated the biological effects (Gamma-H2AX (γ-H2AX) foci and micronucleus (MN) formation) of low-dose X-radiation on the peripheral blood lymphocytes of pediatric (n = 45) and adult (n = 38) participants before and after CT imaging. Participant-specific organ doses were calculated using VirtualDose™CT software, weighted to the corresponding organ's blood volume, summed to derive the blood dose, and then related to induced DNA damage. A significant (p < 0.001) increase in γ-H2AX foci and MN frequencies was observed in both pediatric and adult groups after CT imaging. While the mean effective dose (ED) in pediatric and adult (16.21 ± 11.33 mSv and 31.30 ± 16.25 mSv) participants were significantly different (p < 0.001), the mean blood doses did not differ (9.83 ± 6.34 mGy and 12.82 ± 5.96 mGy) (p > 0.05), respectively. A weak correlation was observed between the induced DNA damage to that of ED and blood dose. The results suggest that damage to blood lymphocytes after CT imaging was observed by an increased γ-H2AX foci result of DNA double-strand breaks. The increase in MN frequency suggests activation of DNA repair, thereby contributing to minimal damage, although they are unstable. Therefore, it is necessary to follow up on the pediatric participants to look for stable aberrations to better relate DNA damage to exposure and long-term health effects, if any.

The Chernobyl nuclear accident of April 1986 remains the most severe nuclear disaster in human history, with long-lasting consequences for ecosystems exposed to chronic ionizing radiation. In the decades since the event, the Chernobyl Exclusion Zone has become an unintended but invaluable natural laboratory for investigating the genetic and ecological effects of persistent radiation exposure. This review synthesizes current knowledge on both immediate and long-term biological consequences observed in plants and animals inhabiting contaminated areas. Initial impacts included acute mortality, reproductive failure, and ecosystem collapse, most notably exemplified by the "Red Forest." Over subsequent years, studies revealed elevated mutation rates, chromosomal aberrations, genomic instability, and heritable genetic damage across diverse taxa. At the same time, evidence of adaptive responses has emerged, including increased antioxidant defenses, epigenetic modifications, and phenotypic changes such as melanism in amphibians. Flora and fauna within the exclusion zone illustrate the dual narrative of vulnerability to mutagenic stress and resilience through evolutionary adaptation. Comparisons with the Fukushima accident demonstrate convergent biological responses across ecosystems while highlighting the importance of context, such as terrestrial versus marine contamination and remediation strategies. Future research must integrate advanced genomic and epigenomic tools, accurate dosimetry, and long-term monitoring to clarify thresholds for harmful versus adaptive outcomes. Chernobyl thus continues to provide critical insights into radiation biology, ecological recovery, and evolutionary toxicology under conditions of chronic environmental stress.

This study investigates chromosomal damage in donkeys to assess the impact of long-term exposure to different concentrations of environmental genotoxic agents, which pose health risks to animals and humans by promoting DNA breaks. The genotoxic damage was assessed through aneuploidy, chromosomal aberrations (CAs), and sister chromatid exchanges (SCEs) tests in donkeys, crossbred Ragusano and Grigio Siciliano breeds, from three areas in the Sicily region (Italy) with different levels of air pollution. Donkeys from areas with higher concentrations of fine particulate matter and nitrogen dioxide showed significantly elevated levels of aneuploidy and chromosomal abnormalities compared to those from less polluted areas. These findings provide the first evidence in donkeys of the combined effects of long-term exposure to airborne pollutants on genomic stability. This study reinforces the potential use of donkeys as effective biomonitoring organisms for evaluating environmental health risks and genotoxic damage under different pollution conditions.

Occupational exposure is a problem that needs to be understood to implement action that prevent diseases. In this cross-sectional study, we monitored the total (116) workers at a battery recycling plant. The objective was to understand if the oxidative biomarkers of lead exposure are of relevance to the functionality of DNA-repair mechanisms. We determined in all of them the Blood Lead Levels (BLL), δ-ALAD activity, lipid peroxidation, DNA damage (alkaline comet assay) and the ability to repair damage induced by ionizing radiation. Our results indicate that Pb-exposed workers exceed the permissible exposure limits and present high values of all variables determined. It was found that BLL and genotoxicity determined in workers show correlation with years worked, δ-ALAD activity and DNA repair capacity, while lipid peroxidation only correlated with BLL. The main result of the study was the detection of elevated oxidative damage in workers exposed to Pb, with no correlation established with the functionality of DNA repair mechanisms (they only repair 50 % of the induced damage). This finding suggests that the oxidative damage generated by Pb partially compromises the genetic stability of these workers, who have worked an average of 5 years at this recycling plant despite exceeding permissible exposure levels. This highlights the need for future studies to determine the induction of systemic homeostasis mechanisms that remain functional in workers, despite their exposure levels.

Cobalt (II, III) oxide nanoparticles (CoO-NPs) have potential applications in different technological and medical fields, including drug delivery and as novel anticancer treatments. However, widespread application could lead to a high-level direct human exposure, raising concerns about their genotoxic potential. This study aimed to evaluate the cytotoxicity and genotoxicity of CoO-NPs in human peripheral blood mononuclear cells (PBMCs) in vitro. Two sizes of CoO-NPs (10-30 nm and < 50 nm) were tested to understand any size-dependent differences in genotoxicity. The study measured NP uptake, reactive oxygen species (ROS) generation, cell viability, DNA strand breaks, micronuclei formation, and sister chromatid exchange to assess the cyto-genotoxic potential of CoO-NPs. Flow cytometric analysis revealed that CoO-NPs with a primary size of < 50 nm were more efficiently internalized by human PBMCs and induced higher ROS levels than 10-30 nm particles. Both nanoparticles' sizes induced significant primary DNA damage at non-cytotoxic concentrations, often in a dose-dependent manner. Cytogenetic analysis demonstrated that CoO-NPs exert genotoxic effects, with < 50 nm NPs inducing more significant DNA damage and reduced cell viability than smaller nanoparticles. Additionally, interindividual differences in response to exposure to CoO-NPs were observed. The study findings suggest that CoO-NPs possess genotoxic potential in human PBMCs in vitro, raising safety concerns about their use. This highlights the need for comprehensive genotoxicity assessments of CoO-NPs in different cell types.

This study aimed to assess the genotoxic effects of chronic occupational exposure to low-dose ionizing radiation among healthcare professionals employed at three hospitals in Aydın, Turkey: Aydın Adnan Menderes University Research and Application Hospital (ADU-UAH), Atatürk State Hospital, and Aydın State Hospital. The exposed group comprised 27 healthcare workers routinely operating in radiation-related departments, while 27 matched individuals with no known exposure constituted the control group.

The induction of telomere dysfunction-related chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) was studied in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). To this end, an EBV-induced lymphoblastoid cell line (T-37) was exposed to increased concentrations of BLM (10-100 µg/mL) for 2 h at 37ºC, and telomere aberrations were analyzed 24 h (first mitosis) after treatment using PNA-FISH with pan-telomeric plus pan-centromeric probes. Telomere signal duplications (TSD) increased significantly in BLM-exposed cells (p < 0.01), although the concentration-response relationship was non-linear. Most of the induced TSD (95-99 %) were of chromatid-type. No induction of telomere signal loss, telomere fusions or telomere associations by BLM was observed in T-37 cells. These findings show that BLM induces short-term telomere dysfunction in EBV-transformed human lymphoblastoid cells in the form of TSD (which implies telomere fragility) and suggest that these effects mainly occur during the G2 stage of the cell cycle. The persistence of this type of aberrations in the long-term in EBV-induced lymphoblastoid cells and other human cells exposed to BLM may be of medical relevance. Telomere fragility induced by BLM could promote genomic instability, which might contribute to the development of secondary tumors in patients undergoing chemotherapy based on this compound. Consequently, our study raises concerns about the potential long-term genomic effects of BLM in treated patients and suggests that the analysis of TSD could be a useful biomarker for detecting BLM-induced telomere dysfunction in human cells.

Error-corrected next-generation sequencing (ecNGS) sensitively detects rare mutations in biological models. We applied Hawk-Seq™ to evaluate chemical-induced mutations using the IVGT TK6 human lymphoblastoid cell line. Since clonal and sub-clonal variants (CVs and SCVs) decrease mutation detection sensitivity, we first identified 4,501,430 CVs compared to GRCh38 by resequencing the TK6 genome. The overall base substitution (BS) frequency in vehicle controls after filtering out these variants was 2.0 × 10 base pairs (bp), relatively higher than in other ecNGS studies. A total of 4974 sites provided the same types of BSs in ≥ 2 vehicle controls, suggesting that SCVs increased the error frequency. After filtering out these sites, the overall background BS frequency significantly decreased (0.93 × 10 bp). Therefore, we filtered out the potential SCV positions identified using resequencing data with increased depth (mean depth of ca. 110), reducing the background overall BS frequency to 0.65 × 10 bp. Finally, we evaluated DNA samples from TK6 cells exposed to N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) for 24 h. The overall BS frequencies in MNU- and ENU-treated samples were 9.0 × 10 and 2.0 × 10 bp, respectively, significantly improving the signal-to-noise ratio. MNU predominantly induced G:C > A:T (21 × 10 bp), 62 times higher than that induced by vehicle controls. ENU primarily induced G:C > A:T (2.7 × 10 bp) and significantly increased A:T > C:G and A:T > G:C frequencies (∼10 bp). Our method sensitively detected mutations, including minor patterns, indicating its potential to reflect various mutagenic mechanisms.

In this study, we investigated the genotoxicity of N-nitrosoproline (NPRO) in human-derived keratinocytes (HaCaT and NCTC2544 cells) using simultaneous UVA irradiation without metabolic activation. NPRO plus UVA exhibited dose- and intensity-dependent micronuclei formation in the keratinocytes, as well as nitric oxide (NO) production. The action spectra of genotoxicity and NO formation from NPRO plus UVA followed the absorption curve of NPRO, indicating that photoenergy was absorbed by the NPRO-triggered photoreaction. A significant increase in cyclic guanosine monophosphate (cGMP) was observed in HaCaT cells treated with NPRO plus UVA. NO production from UVA-irradiated NPRO paralleled micronuclei formation, and the phototoxicity of NPRO may have simultaneously interfered with the cGMP-related signaling systems caused by NO from photoactivated NPRO.

The Ames assay is a bacterial reverse gene mutation test that has been a cornerstone of mutagenicity assessment. The emphasis now is on developing miniaturized versions of the Ames test in Petri dish to require less chemicals, reagents, and liver microsomal S9 fraction, thus reducing the number of test animals needed and to better comply with 3R principles. Miniaturized Ames assay versions promote high throughput testing of multiple samples during compound screening and facilitate the early exclusion of genotoxic agents during the product development process. Existing experimental data shed light on a high concordance between results gained with miniaturized Ames tests and the Petri dish-based method, yet further testing is required to corroborate these findings. We selected compounds with previously reported inconsistent outcomes and assessed their mutagenic potential using two miniaturized Ames assay formats, an agar-based 6-well plate test, and a liquid microplate fluctuation format assay. Investigation of dose-response curves of known mutagens with varying bacterial cell density inputs revealed that the sensitivity of the 6-well agar plate format might be increased by applying the right bacterial cell density. Our analysis indicates an overall good correlation between the results acquired with the two miniaturized Ames assay formats despite the conceptual characteristic differences in the assay paradigms. Furthermore, the miniaturized Ames assay formats could detect several chemicals as positive at lower concentrations than the Petri dish-based assay. Our findings indicate that the miniaturized Ames assay variations show promise as a reliable method for assessing chemical mutagenicity, while also aligning with environmentally friendly testing strategies. Finally, our results show that the miniaturized assays may exhibit increased sensitivity to impurities, potentially contributing to the observed discrepancies in the obtained results.

Chemical risk assessment relies on in vitro genotoxicity tests. Histone modifications (γH2AX and pH3) have emerged as valuable biomarkers for genotoxicity detection. In this study, we compared three parameters (global intensity, nuclear intensity, and foci number) for the γH2AX biomarker and two parameters (global intensity and % cell in mitosis) for the pH3 biomarker. These analyzes were performed in three cell lines: human osteosarcoma U2OS cells, human hepatocellular carcinoma HepG2 cells and rat intestinal epithelial IEC-6 cells. Cells were exposed for 24 h to four well-characterized hazardous substances: nocodazole (aneugen), etoposide (topoisomerase inhibitor), benzo[a]pyrene (DNA adducts inducer), and tunicamycin (apoptosis inducer). The Benchmark Concentration (BMC) approach indicated that the sensitivity of the technics varied depending on both the chemical compounds and the tested cell line. The γH2AX foci analysis provided the higher sensitivity for clastogenic compounds. For the aneugenic compound, the global intensity and the proportion of mitotic cells showed similar sensitivity. Following tunicamycin treatment, we only detected increase in γH2AX nuclear intensity in U2OS cell model, indicating that apoptosis does not interfere with γH2AX global intensity or foci number, thereby minimizing the risk of false positive results. Finally, we observed that compared to the other methods, global intensity permitted to monitor weaker fold inductions of the biomarkers. By comparing the different quantification methods of histone modifications used as genotoxicity biomarkers, this study highlights the most suitable parameters to be used.

Systemic lupus erythematosus (SLE) is a persistent autoimmune inflammatory disease associated with an elevated risk of kidney damage. The etiology of SLE remains unclear; nevertheless, current investigations increasingly indicate that increased DNA damage and deficiencies in the mechanisms of its repair might contribute to its pathogenesis, necessitating the identification and management of the disease. Therapies for SLE have improved considerably over recent decades. However, drugs that specifically address the underlying pathogenic pathways, such as potential DNA repair deficiencies, are unavailable. In this situation, drugs that ameliorate the altered DNA damage/repair might be a possible option for treating SLE. We investigated whether GW0742, an agonist of the peroxisome proliferator activator receptor β/δ, improves kidney function and ameliorates DNA damage/repair alteration in female lupus-prone mice. The results demonstrate that the repeated administration of GW0742 significantly ameliorates DNA damage/repair alteration in the bone marrow cells of lupus-prone animals, as assessed by the comet test. Furthermore, the administration of GW0742 restored the impaired DNA damage/repair pathway in lupus-prone mice by decreasing Gadd45a and p53 expression while elevating Ogg1 and Parp1 in the kidney tissues. The administration of GW0742 recovered the disturbed kidney redox balance in lupus-prone mice. It also ameliorated the altered biochemical markers related to lupus nephritis, as demonstrated by reduced levels of urinary protein and albumin, serum creatinine, and BUN. GW0742's protective outcome was verified by its ability to diminish the increased inflammatory marker MPO activity and ameliorated kidney histological characteristics of SLE. This suggests that GW0742 is a promising novel therapeutic agent for managing SLE and its associated complications.

Some occupational exposures to pesticides have been associated with genotoxicity which arises from DNA single-strand breaks (SSBs), repair of DNA double-strand breaks (DSBs), DNA adduct formation, or DNA-DNA and DNA-protein cross-links. Polymorphisms in genes encoding enzymes of DNA repair pathways may modulate the individual's susceptibility to pesticide-induced genotoxicity. A total of 450 subjects were included in this study, which comprises 225 agricultural workers exposed to complex mixtures of pesticides and 225 non-exposed controls from Punjab, North-West India. Susceptibility of OGG1 Ser326Cys (C1245G), XRCC1 Arg194Trp (C26304T), XRCC1 Arg399Gln (G28152A), XPC Lys939Gln (A2920C), XPC Ala499Val (C21151T), XPD Asp312Asn (G23591A), XPD Lys715Gln (A35931C), XPF Arg415Gln (G1244A), XPG Asp1104His (G3507C), ERCC1 3'-UTR (C8092A) and ERCC1 Asn118Asn (C354T) gene polymorphisms with pesticide-induced DNA damage was determined by Kruskal-Wallis test. The association of epistatic gene interactions with DNA damage was studied by ANOVA. The results indicated significant interactions of variant OGG1 326Ser/Cys genotype with XRCC1 194Arg/Trp and XRCC1 399Arg/Gln genotypes in increased susceptibility to DNA damage. XPC 939Gln/Gln genotype significantly interacts with XPC 499Ala/Val, XPD 312Asp/Asp and XPD 715Gln/Gln variant genotypes to increase DNA damage susceptibility. Among exposed XPF 415Gln/Gln individuals, DNA damage was significantly higher in those individuals who had variant XPG Asp/His and ERCC1 8092CA genotypes. We observed some statistically significant epistatic gene interactions in DNA repair pathways in modulating DNA damage, which may be used as biomarkers of susceptibility in pesticide-exposed agricultural workers of Punjab, North-West India.

The SOS response contains a set of about 45 genes related to the repair or tolerance to DNA damage. These genes are normally blocked but when lesions upon the genetic material occur an SOS signal is generated allowing their expression. Most types of DNA lesions must be modified or processed to induce SOS. In a previous work, a model was proposed suggesting the possible paths that could be followed from the different types of lesions to the induction of the response. One of these possible routes is through the base excision repair mechanism (BER). Since in E. coli the AP endonuclease exonuclease III plays a key role in this repair pathway, in the present study we evaluate the participation of xthA product in the processing of DNA lesions made by gamma rays, UV-C light, ethyl methanesulphonate, methyl methanesulphonate, mitomycin C, hydrogen peroxide and tert-buthylhydroperoxide to trigger the SOS response. A strain defective in xthA and a wt strain were exposed to different genotoxic agents and survival and SOS induction were analyzed. The results show differences in the survival and SOS induction to each genotoxic agent between the wt strain and the xthA mutant; depending on the type of DNA damage inflicted, the SOS response level was either higher or lower compared to the wt strain. This suggests that while the AP endonuclease role of exonuclease III enzyme suppresses SOS induction when bulky and methylated lesions occur, it enhances SOS induction when the damage is generated by ROS, in agreement with a previously proposed model.