No abstract

alpha-Endosulfan and ss-endosulfan are isomers of endosulfan, a pesticide used worldwide. In this study, we examined the genotoxicity of [alpha]- and ss-endosulfan in vitro with a HepG2 cell line. We used sister chromatid exchanges (SCE), micronuclei (MN), and DNA strand breaks as detected by single-cell gel electrophoresis (SCG) assays as biomarkers to judge the genotoxicity of [alpha]- and ss-endosulfan at concentrations from 1 times 10(-12) M to 1 times 10(-3) M. After treating HepG2 cells for 48 hr with ss-endosulfan, SCE showed a significant increase at concentrations from 1 times 10(-7) M to 1 times 10(-5) M, and MN showed a significant increase at concentrations from 5 times 10(-5) M to 1 times 10(-3) M. [alpha]-Endosulfan failed to show significant effects in both the SCE and MN assays. After treating HepG2 cells with [alpha]- or ss-endosulfan for 1 hr, DNA strand breaks were significantly induced by [alpha]-endosulfan at concentrations from 2 times 10(-4) M to 1 times 10(-3) M, and by ss-endosulfan at 1 times 10(-3) M. The results of this study suggest that both [alpha]- and ss-endosulfan are genotoxic to HepG2 cells and that the genotoxicity of ss-endosulfan seems stronger than that of [alpha]-endosulfan.

X-ray repair crosscomplementing group 1 (XRCC1) has a central role in base excision repair (BER) and single-strand break repair (SSBR). XRCC1 gene polymorphisms (codons 194, 280, and 399) have been identified, and in some cases have been reported to contribute to variations in DNA repair capacity and susceptibility to cancer. To further characterize the effects of XRCC1 gene polymorphisms and their possible interactions with environmental factors on individual levels of DNA damage, we investigated the XRCC1 genotypes of 222 healthy Japanese workers and analyzed data with respect to smoking, drinking habits, age, and health practice index (HPI). Our results showed that poor HPI would associate with a higher level of tail moment (TM). Individuals with one or two XRCC1(R280H) variant alleles exhibited significantly higher TM values, and these differences were enhanced by alcohol consumption and aging, whereas smoking and poor HPI may cover up the differences. On the other hand, using a stratified analysis, we found that the XRCC1(R194W) variant was associated with a higher TM value in the 40-50 year-old age group, and the XRCC1(R399Q) variant was associated with a lower TM value in the < or =20 pack-years group or in the 40-50 year-old age group. These data suggest that XRCC1 polymorphisms could influence individual DNA repair capacity by interacting with lifestyle factors, and specifically, the data indicated that the XRCC1(R280H) allele may be more important than codon 194 or 399 alleles.

Single-cell gel electrophoresis (SCG) is a simple, sensitive and effective technique. Being able to reflect quantitatively the genotoxicity of many hazardous agents, it is promising for application in environmental genotoxic monitoring and the study of carcinogenesis. In clinics, it can be used to evaluate the DNA repair ability and monitor DNA breaks during cancer therapy. As a biomarker, it has its own merits and limitations, being different from other biomarkers such as sister chromatid exchange (SCE) test and micronudei (MN) assay. In many studies, it is more sensitive than SCE or MN.Combination studies with other biomarkers like SCE, MN, chromosomal aberration, bcl-2 and genetic polymorphisms have begun to demonstrate its great importance for the understanding of carcinogenesis and the genotoxicities of environmental factors.

(-)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main ingredient of green tea extract. Although the anti-carcinogenic and cancer inhibitory effects of EGCG have been widely reported, its genotoxicity is not clear and seldom reported. In this study, we examined the effects of EGCG on DNA strand breaks in the isolated lymphocytes and whole blood lymphocytes obtained from two smoking subjects and a nonsmoking healthy subject using a single cell gel electrophoresis (SCG) assay. The results showed that after 2 hrs of treating the isolated lymphocytes from the smokers, EGCG induced a significant, increase in DNA strand breaks at concentrations from 2.5×10(-5) M to 2.0×10(-4) M, while after 2 hrs of treating the whole blood obtained from the same smokers, EGCG suppressed the DNA strand breaks in the lymphocytes at concentrations of 1.0×10(-4) M and 2.0×10(-4) M. A similar suppressive result was also shown in the whole blood lymphocytes from the nonsmoker at nearly the same concentrations, while at concentrations of 1.0×10(-3) M or 2.0×10(-3) M, EGCG induced a significant increase in DNA strand breaks in the whole blood lymphocytes from the nonsmoker. This result suggests that EGCG is not only inhibitory against DNA strand breaks in whole blood, but also genotoxic to the isolated or whole blood lymphocytes at high concentrations. Thus, more research is needed to comprehensively assess the effects of EGCG on genetic materials.