Carcinogenesis, Vol. 21, No. 7, 1355-1363,
July 2000
© 2000 Oxford University Press
Carcinogenesis |
Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol
1 Developmental Endocrinology Section, Reproductive Toxicology Group, Laboratory of Toxicology, Environmental Toxicology Program and
2 Biostatistics Branch, Environmental Diseases and Medicine Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709,
3 Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Prenatal exposure to diethylstilbestrol (DES) is associated with reproductive tract abnormalities, subfertility and neoplasia in experimental animals and humans. Studies using experimental animals suggest that the carcinogenic effects of DES may be transmitted to succeeding generations. To further evaluate this possibility and to determine if there is a sensitive window of exposure, outbred CD-1 mice were treated with DES during three developmental stages: group 1 was treated on days 9–16 of gestation (2.5, 5 or 10 µg/kg maternal body weight) during major organogenesis; group II was treated once on day 18 of gestation (1000 µg/kg maternal body weight) just prior to birth; and group III was treated on days 1–5 of neonatal life (0.002 µg/pup/day). DES-exposed female mice (F1) were raised to maturity and bred to control males to generate DES-lineage (F2) descendants. The F2 males obtained from these matings are the subjects of this report; results in F2 females have been reported previously [Newbold et al. (1998) Carcinogenesis, 19, 1655–1663]. Reproductive performance of F2 males when bred to control females was not different from control males. However, in DES F2 males killed at 17–24 months, an increased incidence of proliferative lesions of the rete testis and tumors of the reproductive tract was observed. Since these increases were seen in all DES treatment groups, all exposure periods were considered susceptible to perturbation by DES. These data suggest that, while fertility of the DES F2 mice appeared unaltered, increased susceptibility for tumors is transmitted from the DES `grandmothers' to subsequent generations.
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