An advance Cytogenetic approach for the determination of mutagenic potential of chemicals that induce Cell arrest in G2 phase by application of premature chromosome condensation (PCC) in peripheral blood lymphocytes

S.I. Malik

Abstract


Several studies have been carried out to evaluate the mutagenic and carcinogenic potential of atrazine, the most prevalent of triazine herbicides classified as a “possible human carcinogen” The majority of these studies have been negative but positive responses have been also reported including mammary tumers in female Sprague-Dawley rats.Sister chromatid exchanges (SCEs) caused by the presence of DNA lesions at the moment of DNA replication, have been reported. Even though exposures to higher concentration of altrazine could provide clear evidence for its genotoxicity, conventional SCE analysis at metaphase cells cannot be used because affectet cells are delayed in G2-phase and do not proceed to mitosis. As a result, the genotoxic potential of altrazine may have been underestimated. Since clear evidence has been recently reported relating SCEs to homologous recombinational events, we are testing here the hypothesis that high concentration of altrazine will cause a dose-dependent increase in homologous recombinational events as quantified by the frequency of SCEs analyzed in G2-phase prematurely condensed chromosomes (PCCs). The methodology enables the visualization of SCEs in G2-blocked cells and is based on drug-induced PCCs in cultured lymphocytes. The result obtained for high concentration of atrazine; do not demonstrate a dose-depended increase in homologous recombination events. They do not support, therefore, atrazine genotoxic mode of action. However, they suggest that an important part in the variation of SCE frequency reported by different laboratories when conventional SCE analysis is applied after exposure to a certain concentration of atrazine is due to differences in cell cycle kinetics of cultured lymphocytes than to a true biological variation in the cytogenetic end point used.

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