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ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO
Citation:
Fenton, S E. AND C C. Davis. ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO.
SE Fenton and CC Davis
Reproductive Toxicology Division, NHEERL, ORD, USEPA, Durham, NC, USA
Recently, we found that ATR exposure during mammary bud outgrowth (late gestation) delays normal postnatal epithelial progression in Long Evans (LE) to a greater extent than in Sprague Dawley (SD) rats. To determine if ATR-induced developmental delays alter susceptibility of LE
females to mammary carcinogen, we gavaged time-pregnant LE (10/treatment) and SD (11-15/treatment) dams with 0, 12.5, 25, or 50 mg ATR/kg body weight (2X/day) on gestation days 15-19. The female offspring were gavaged with dimethylbenz[a]anthracene (30 mg/kg) on postnatal day 45, a time when mammary glands have largely matured in controls. Animals were evaluated for palpable tumors weekly and killed 18 and 24 weeks later. SD offspring exposed to 0, 12.5, 25, and 50 mg ATR/kg (respectively) had overall mammary tumor incidences of 40, 25, 52, and 52% (c2, p=0.15). Their tumor latency (20, 22, 21, and 22 weeks), multiplicity (2.25, 2.4, 2.9, and 1.5 tumors/tumor-bearing animal), and tumor volumes (3.05, 5.63, 1.81, and 1.08 cm3) were unchanged by gestational ATR. In contrast, LE offspring exposed to 0, 12.5, 25, and 50 mg ATR/kg had overall mammary tumor incidences of 41, 45, 62, and 60% (c2, p=0.04). Although LE displayed no decrease in tumor latency (20.0, 21.6, 18.3, and 21.7 weeks), they had increased multiplicity (1.1, 1.5, 1.7, and 2.0) and larger tumor volumes (0.8, 0.2, 1.3, and 13.4 cm3, p=0.04) following ATR in utero. Further, LE (but not SD) rats had significant increases in the percentage of animals with abnormalities in additional organs compared to controls (i.e, adrenal nodules, pituitary foci, ovarian cysts>2mm, and lymph node and spleen enlargement) at all ATR doses tested (p<0.05). Our data demonstrate that by delaying mammary gland development, gestational ATR exposure increases the susceptibility of the LE female to carcinogen, perhaps by extending the period of vulnerability. (This abstract does not necessarily reflect EPA policy).