Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells.
Some environmental estrogen-like compounds, such as bisphenol A (BPA), 4-nonylphenol (NP), 4-octylphenol (OP), propyl p-hydroxybenzoate (P-PHBA), and butyl p-hydroxybenzoate (B-PHBA), synthetic estrogen, diethylstilbestrol (DES), and natural estrogen, 17beta-estradiol (E2), were studied for their genotoxicity in CHO-K1 cells using sister-chromatid exchange (SCE), chromosome aberration (CA), and DNA strand break (comet) assays. Six of the chemicals, excluding E2, caused DNA migration in the comet assay and induced SCEs at one or more of the highest doses. Among the chemicals, OP produced an especially high incidence of SCEs. Structural CA was induced by five of the chemicals, excluding OP and NP, and BPA, E2, and DES also induced aneuploid cells. E2 and DES particularly increased the rate of polyploidy at high doses. The incidence of colchicine-mitosis-like (c-mitotic) figures suggesting spindle disrupting effects was also detected with five of the chemicals, excluding OP and NP, and six of the chemicals, excluding E2, caused endoreduplication (ERD), a form of nuclear polyploidization induced by block of cell cycle at G2 phase, at one or more high doses. Our present results suggest that OP and NP cause repairable DNA damage, including SCEs, and do not result in CA, while the damage caused by DES, BPA, P-PHBA, and B-PHBA results in the induction of CAs together with SCEs probably because of imperfect repair. We are unable to explain the observation that the DNA damage caused by E2 resulted in CA induction but not DNA migration or SCE induction, except for speculating that the DNA damage is different from that caused by DES and the estrogen-like chemicals. Our findings also suggest that E2, DES and BPA have aneuploidogenic properties, and that the former two of chemicals also are polyploidy-inducing agents.
Tayama
Sumiko
S
Department of Toxicology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan. Sumiko_Tayama@member.metro.Tokyo.jp
Nakagawa
Yoshio
Y
Tayama
Kuniaki
K
D000818:Animals; D001559:Benzhydryl Compounds; D016466:CHO Cells; D002869:Chromosome Aberrations / Q000187:drug effects*; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000633:toxicity; D045166:Estradiol Congeners / Q000633:toxicity; D004967:Estrogens / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests; D010226:Parabens / Q000633:toxicity; D010636:Phenols / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D004958:Estradiol; D045166:Estradiol Congeners; D004967:Estrogens; D010226:Parabens; D010636:Phenols; C080417:4-octylphenol; C041594:4-nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C006068:propylparaben