Genotoxic Effect of Atrazine, Arsenic, Cadmium and Nitrate, Individually and in Mixtures at Maximum Contaminant Levels on mammalian Breast Cell Lines

Abstract

There is strong evidence that hormonally active agents (HAAs) such as Atrazine (ATZ), Cadmium (Cd), Arsenic (As) and Nitrate (NO₃) have both estrogenic activity and carcinogenic potential. Atrazine has clastogenic effects and may also act as tumor promoter as it induces the aromatase enzyme. Arsenic and Cadmium have been implicated in the etiology of skin, lung, prostate and liver cancers. Nitrate in drinking water has been found to increase the risk of bladder cancer.

This study examined the genotoxicity of the aforementioned HAAs alone and in mixtures using mammalian breast cell lines, MCF-7 and MCF-10A, which are estrogen receptorpositive (ER+) and estrogen receptor-negative (ER-), respectively. To study the clastogenic potential by whole cell and flow karyotype damage, cells were exposed to environmentally relevant concentrations of ATZ, Cd, As and NO₃ for 4 and 7 days.

Results indicated that all treatments induced whole cell clastogenicity in MCF-7 cells; except Cd and NO3 after 4 and 7 days as well as the 10% quaternary As mixture after 1 week. In MCF-10A cells, all treatments except the 10% mixture induced whole cell clastogenicity after 4 days, where flow karyotype damage was detected in all treatments except for the 10% mixture after 1 week. Estrogen caused whole cell damage but not flow karyotype damage in MCF-7. On the other hand, estrogen caused flow karyotype damage and not whole cell damage in MCF-10A cells, suggesting that estrogen receptor modulated the genotoxicity of estrogen. Cd caused flow karyotype damage but not whole cell damage in MCF-7 indicating that Cd’s gentoxicity is not related to its estrogenic activity.

Keywords: HAAs, clastogenicity, flow-karyotype, genotoxicity, MCF-7, MCF-10A