Formation of adducts by bisphenol A, an endocrine disruptor, in DNA in vitro and in liver and mammary tissue of mice

Abstract

Endocrine disruptors (EDs) represent a major toxicological and public health issue, and the xenoestrogen bisphenol A (BPA) has received much attention due to its high production volume and widespread human exposure. Also, due to its similarity to diethylstilbestrol, a known human carcinogen, BPA has been investigated for its genotoxic and carcinogenic properties, but the results have been either inconclusive or controversial. Metabolically activated BPA has previously been shown to form DNA adducts both in vitro and in rat liver. The present study was designed (a) to assess the sensitivity threshold of DNA-adduct detection by 32P-postlabelling in an acellular system and (b) to evaluate the formation of DNA adducts in both liver and mammary cells of female CD-1 mice receiving BPA in their drinking water (200 mg/kg body weight) for eight consecutive days. The reaction of BPA with calf thymus DNA, in the presence of S9 mix, resulted in a dose-dependent formation of multiple DNA adducts, with a detection limit of ∼10 ng of this ED under our experimental conditions. Administration of BPA to mice confirmed that DNA adducts are formed in liver (3.4-fold higher levels than in controls). In addition, new evidence is provided that DNA adducts are formed in target mammary cells (4.7-fold higher than in controls). Although DNA adducts do not necessarily evolve into tumours or other chronic degenerative diseases, the formation of these molecular lesions in target mammary cells may bear relevance for the potential involvement of BPA in breast carcinogenesis.