title: Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor.
abstract: Bisphenol A (BPA) is a well-known endocrine disruptor (ED) which represents a major toxicological and public health concern due to its widespread exposure to humans. BPA has been reported to induce DNA adduct and aneuploidy in rodents. Recent studies in humans depicted its association with recurrent miscarriages and male infertility due to sperm DNA damage indicating that BPA might have genotoxic activity. Hence, the present study was designed to determine genotoxic and mutagenic effects of BPA using in-vivo and in-vitro assays. The adult male and female rats were orally administered with various doses of BPA (2.4 μg, 10 μg, 5mg and 50mg/kgbw) once a day for six consecutive days. Animals were sacrificed, bone marrow and blood samples were collected and subjected to series of genotoxicity assay such as micronucleus, chromosome aberration and single cell gel electrophoresis (SCGE) assay respectively. Mutagenicity was determined using tester strains of Salmonella typhimurium (TA 98, TA 100 and TA 102) in the presence and absence of metabolically active microsomal fractions (S9). Further, we estimated the levels of 8-hydroxydeoxyguanosine, lipid per-oxidation and glutathione activity to decipher the potential genotoxic mechanism of BPA. We observed that BPA exposure caused a significant increase in the frequency of micronucleus (MN) in polychromatic erythrocytes (PCEs), structural chromosome aberrations in bone marrow cells and DNA damage in blood lymphocytes. These effects were observed at various doses tested except 2.4 μg compared to vehicle control. We did not observe the mutagenic response in any of the tester strains tested at different concentrations of BPA. We found an increase in the level of 8-hydroxydeoxyguanosine in the plasma and increase in lipid per-oxidation and decrease in glutathione activity in liver of rats respectively which were exposed to BPA. In conclusion, the data obtained clearly documents that BPA is not mutagenic but exhibit genotoxic activity and oxidative stress could be one of the mechanisms leading to genetic toxicity.
authors.affiliation: National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health, J.M. Street, Parel, Mumbai 400012, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Tiwari
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kamble
authors.forename: Swapnil
authors.initials: S
authors.lastname: Chilgunde
authors.forename: Prakash
authors.initials: P
authors.lastname: Patil
authors.forename: Girish
authors.initials: G
authors.lastname: Maru
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Kawle
authors.forename: Uma
authors.initials: U
authors.lastname: Bhartiya
authors.forename: Lebana
authors.initials: L
authors.lastname: Joseph
authors.forename: Geeta
authors.initials: G
authors.lastname: Vanage
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002273:Carcinogens; D052244:Endocrine Disruptors; D009153:Mutagens; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds