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Mammary gland development and response to prenatal atrazine exposure in the Sprague Dawley and Long-Evans rats.
Citation:
WOLF, C. J., J. STANKO, AND S. E. FENTON. Mammary gland development and response to prenatal atrazine exposure in the Sprague Dawley and Long-Evans rats. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
The purpose of this study was to assess the differences in MG development of female offspring of vehicle and ATR-exposed LE and SD rats.
Description:
Mammary gland (MG) tumor development in Sprague Dawley (SD) rats is increased by longterm dietary exposure to the chlorotriazine herbicide atrazine (ATR). ATR is proposed to cause these changes in the adult SD rat by altering hormonally-regulated estrous cyclicity. In Long-Evans (LE) rats, both puberty and MG development are delayed by briefprenatal ATR exposure. Prenatal exposure has not been tested in SD rats. We have observed that dimethylbenz[a]anthracene (DMBA) treatment results in a greater incidence ofMG tumors in LE compared to SD rats and ~e hypothesize that this increased susceptibility is due to strain differences in the rate of MG differentiation, and that these differences are compounded by exposure to ATR. The purpose ofthis study was to assess the differences in MG development of female offspring ofvehicle and ATR-exposed LE and SD rats. Timed-pregnant LE and SD rats (n=9/treatment group) were orally gavaged with 0, 12.5, 25, or 50 mg ATR/kg body weight 2x/dayon gestational days 15-19. Mammary glands were collected from female offspring on PND 4, 25, 33, and 45 and MG whole mounts were scored according to previously established developmental criteria. MG development was delayed by ATR on PND4 and PND25 in the SD rat at 50 mglkg, and at PND 33 in both strains at 25 and 50 mglkg (p< 0.05). At PND 45, MG differentiation was delayed in both strains at all doses (12.5 mglkg, p< 0.01 in LE, p< 0.05 in SD; 25 mg/kg, p< 0.01 in LE, p< 0.001 in SD; 50 mglkg, p< 0.001 in LE and SD). Additionally, MG ofSD offspring were much more developed than that ofLE offspring at respective ages, although age at VO was not different between strains. In summary, ATR delayed MG development in both LE and SD with a LOAEL of25 mglkg/day (12.5 mg/kg/dose), despite the difference in MG maturity between the strains. These data suggest less developed MG in the LE may render this strain more susceptible to DMBA-induced tumor promotion. This abstract does not necessarily reflect EPA policy.