Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse.
Bisphenol A (BPA) is a synthetic monomer widely used to polymerize polycarbonate plastics and resins. It is shown in vitro to interfere with microtubules, producing aberations in mitotic and meiotic spindles. An increase of meiotic abnormalities in untreated female mice from an experimental colony was temporally correlated with the accidental release of BPA from polycarbonate cages and bottles damaged by inadvertent treatment with harsh alkaline detergents [P.A. Hunt, K.E. Koehler, M. Susiarjo, C.A. Hodges, A. Ilagan, R.C. Voigt, S. Thomas, B.F. Thomas, T.J. Hassold, Bisphenol A exposure causes meiotic aneuploidy in the female mouse, Curr. Biol. 13 (2003) 546-553]. In the present study, potential aneugenic effects of BPA on mouse male and female germ cells and bone marrow cells have been evaluated after acute, sub-chronic or chronic in vivo exposure. Female mice were orally treated with a single BPA dose, with 7 daily administrations or exposed for 7 weeks to BPA in drinking water. No significant induction of hyperploidy or polyploidy was observed in oocytes and zygotes at any treatment condition. The only detectable effect was a significant increase of metaphase II oocytes with prematurely separated chromatids after chronic exposure; this effect, however, had no irreversible consequence upon the fidelity of chromosome segregation during the second meiotic division, as demonstrated by the normal chromosome constitution of zygotes under the same exposure condition. With male mice, no delay of meiotic divisions was found after six daily oral doses of BPA with the BrdU assay. Similarly, no induction of hyperploidy and polyploidy was shown in epydidimal sperm hybrized with probes for chromosomes 8, X and Y, 22 days after six daily oral BPA doses. Finally, two daily oral BPA doses did not induce any increase of micronucleus frequencies in polychromatic erythrocytes of mouse bone marrow. In conclusion, our results do not add evidence to the suspected aneugenic activity of BPA and suggest that other factors or co-factors should be considered to explain the unexpected burst of meiotic abnormalities previously attributed to accidental BPA exposure.
Pacchierotti
F
F
Section of Toxicology and Biomedical Sciences, ENEA CR Casaccia, Via Anguillarese 301, 00123 Rome, Italy. pacchier@casaccia.enea.it
Ranaldi
R
R
Eichenlaub-Ritter
U
U
Attia
S
S
Adler
I-D
ID
D024422:Aneugens / Q000633:toxicity*; D000782:Aneuploidy; D000818:Animals; D001559:Benzhydryl Compounds; D005260:Female; D005854:Germ Cells / Q000187:drug effects* / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D015162:Micronucleus Tests / Q000379:methods; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011123:Polyploidy; D015053:Zygote / Q000187:drug effects / Q000378:metabolism; D000098826:Bisphenol A Compounds
D024422:Aneugens; D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds