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Strain Differences in Dimethylbenz[a]anthracene-Induced Mammary Tumor Incidence in Long Evans and Sprague Dawley Rat Offspring Following Prenatal Atrazine Exposure
Citation:
STANKO, J., C. C. DAVIS, AND S. E. FENTON. Strain Differences in Dimethylbenz[a]anthracene-Induced Mammary Tumor Incidence in Long Evans and Sprague Dawley Rat Offspring Following Prenatal Atrazine Exposure. Presented at American Association for Cancer Research (AACR), Denver, CO, April 18 - 22, 2009.
Impact/Purpose:
This work evaluates the differences in mammary gland development and tumor susceptibility in two commonly used strains of rat. It also addresses the dose responsiveness of these endpoints to a commonly used herbicide, atrazine, which is currently under re-evaluation under its iRED by OW and OPPTS. Our results show that when tumor formation is stimulated by the chemical carcinogen DMBA, there are differences in incidence of tumor formation in response to prenatal exposure to atrazine in the Long-Evans rat and not the Sprague Dawley.
Description:
It has been shown that prenatal exposure to the chlorotriazine herbicide atrazine (ATR) during mammary bud outgrowth (late gestation) delays postnatal mammary epithelial progression in Long Evans (LE) rats. Our laboratory has recently found that prenatal exposure to ATR also effects postnatal mammary gland development in Sprague Dawley (SD) rats. To determine if ATR-induced developmental delays alter susceptibility to mammary carcinogenesis, timed-pregnant LE (>10/treatment) and SD (>20/treatment) dams were gavage dosed with 0, 12.5, 25, or 50 mg ATR/kg body weight (BW) 2x/day on gestation days 15-19. Female offspring were then gavage dosed with 30 mg dimethylbenz[a]anthracene (DMBA)/kg BW on postnatal day 45, a time when mammary glands have largely matured in untreated animals. Animals were palpated weekly for mammary tumors and necropsied at 18 or 24 weeks following DMBA treatment. All values are reported as means ± standard error and animals were considered individually in statistical analyses as DMBA exposure was conducted post-weaning. Statistical differences were assessed by either ANOVA or trend analysis. SD offspring exhibited overall mammary tumor incidences of 40, 24, 52, and 52% (p=0.07) in the 0, 12.5, 25, and 50 mg ATR/kg BW treatment groups, respectively. Mammary tumor latency (time to first palpable tumor following DMBA treatment; 18.3 ± 1.8, 22.0 ± 2.0, 17.5 ± 1.4, 20.9 ± 1.1 weeks), mean number of tumors/treatment group (0.9 ± 0.3, 0.6 ± 0.3, 1.5 ± 0.3, 0.8 ± 0.3), tumor multiplicity (2.3 ± 0.5, 2.4 ± 0.5, 2.9 ± 0.7, 1.5 ± 0.3 tumors/tumor bearing animal), and tumor volume (1.3 ± 0.7, 1.6 ± 1.5, 1.6 ± 0.9, and 0.4 ± 0.1 cm3) were unchanged by ATR treatment compared to controls. In contrast, LE offspring exhibited mammary tumor incidences of 38, 45, 62, and 60% (p=0.05) in the 0, 12.5, 25, and 50 mg ATR/kg BW treatment groups, respectively. Although mammary tumor multiplicity (1.1 ± 0.1, 1.5 ± 0.2, 1.7 ± 0.3, and 2.0 ± 0.5 tumors/tumor bearing animal; p=0.06) was not significantly increased, there was a dose-related increase in the number of animals with more than one tumor (5, 18, 24, and 30%; p<0.05) and the mean number of tumors/treatment group was greater in the 25 mg ATR/kg BW (1.1 ± 0.2; p<0.05) and 50 mg ATR/kg BW (1.2 ± 0.3; p<0.05) compared to control animals (0.4 ± 0.2). Tumor latency (20.3 ± 1.6, 21.0 1.0, 18.6 ± 1.5, 19.8 ± 2.2 weeks) and tumor volume (0.9 ± 0.5, 0.3 ± 0.2, 0.7 ± 0.4, and 19.4 ± 15.7 cm3) were unchanged in LE offspring following prenatal exposure to ATR. These data suggest that ATR-induced delays in mammary gland development may increase the susceptibility of LE rats to mammary carcinogenesis, more so than in SD rats. (This abstract does not necessarily reflect EPA policy).