Mammalian cell transformation and aneuploidy induced by five bisphenols

Abstract

Bisphenol‐A (BP‐A), a monomer of plastics used in numerous consumer products and a xenoestrogen, induces cellular transformation and aneuploidy in Syrian hamster embryo (SHE) cells. In this study, the abilities of 4 other bisphenols to induce cellular transformation and genetic effects in SHE cells were examined and compared to BP‐A. Cellular growth was inhibited by all bisphenols in a concentration‐related manner. The growth inhibitory effect of the bisphenols ranked: BP‐5 > BP‐4 > BP‐3 > BP‐2 or BP‐A. Morphological transformation of SHE cells was induced by BP‐A, BP‐3, BP‐4 and BP‐5, and the induced‐transformation frequencies were highest with BP‐4. None of the bisphenols induced gene mutations at the Na+/K+ ATPase locus or the hprt locus, or chromosomal aberrations in SHE cells. By contrast, aneuploidy induction in the near‐diploid range was exhibited by BP‐A, BP‐3, BP‐4 or BP‐5, corresponding to the transforming activity of each compound. The results indicate that BP‐A, BP‐3, BP‐4 and BP‐5 exhibit transforming activity in SHE cells, while BP‐2 does not, and that aneuploidy induction may be a causal mechanism of the transforming activity. Int. J. Cancer 86:151–154, 2000. © 2000 Wiley‐Liss, Inc.

Effect of prenatal exposure to bisphenol a on the vagina of albino rats: immunohistochemical and ultrastructural study

“…The carcinogenic potential of BPA has been studied in vitro. High doses of BPA have induced cell-transforming activities and aneuploidy in Syrian hamster embryo cells, suggesting that it has the potential to be genotoxic [35]. Antigen Ki-67 is a nuclear protein that is associated with cellular proliferation [7].…”

Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants

“…As a result of the oxidative metabolism of estrogens, undesired products can be formed and have altered hormonal activity and can chemically react with and damage DNA (2)(3)(4)(5). Sequential accumulation of genetic alterations resulting from damage to DNA can result in the activation of oncogenes and͞or inactivation of tumor suppressor genes (6).…”

“…Sequential accumulation of genetic alterations resulting from damage to DNA can result in the activation of oncogenes and͞or inactivation of tumor suppressor genes (6). Recent reports suggest that endogenous estrogenic hormones or their metabolites can promote breast cancer carcinogenesis (2,4,7,8). Initially, such hypotheses were based on the fact that high serum levels and long exposure (early menarche and late menopause) to estrogens were associated with higher incidence of breast cancer (9,10).…”

Bisphenol A: Understanding Its Health Effects from the Studies Performed on Model Organisms

“…This inding suggests that exposure to BPA during the time that meiosis resumes in the mid-cycle surge by luteinizing hormone (LH) can result in an increase in foetal aneuploidy and subsequent spontaneous abortion in humans [47]. The efect of BPA on aneuploidy has also been examined in cell culture [48][49][50][51]. In the study by Tsutsui et al [48,49] embryo cells with BPA (100 μM) for 48 hours resulted in statistically signiicant increases in the percentage of aneuploid metaphases with chromosome losses.…”

“…The efect of BPA on aneuploidy has also been examined in cell culture [48][49][50][51]. In the study by Tsutsui et al [48,49] embryo cells with BPA (100 μM) for 48 hours resulted in statistically signiicant increases in the percentage of aneuploid metaphases with chromosome losses. Reports are also available that revealed delay in the meiotic cell cycle, possibly by a mechanism that degrades centrosomal proteins and thus perturbs the spindle microtubule organization and chromosome segregation in mouse oocyte during meiosis.…”