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STRAIN-DEPENDENT SUSCEPTIBILITY TO TRANSPLACENTALLY-INDUCED MURINE LUNG TUMORS AND DNA ADDUCTS OF 3-METHYLCHOLANTHRENE
Citation:
Nelson, G B., J A. Ross, J. E. Moore, M. Xu, N. D. Kock, AND M. S. Miller. STRAIN-DEPENDENT SUSCEPTIBILITY TO TRANSPLACENTALLY-INDUCED MURINE LUNG TUMORS AND DNA ADDUCTS OF 3-METHYLCHOLANTHRENE. Presented at AACR, Orlando, FL, March 27-31, 2004.
Description:
Strain-dependent susceptibility to transplacentally-induced murine lung tumors and DNA adducts of 3methylcholanthrene G B Nelson, J A Ross, J E Moore, M Xu, N D Kock, M S Miller Wake Forest University, Winston-Salem, NC and USEPA, Research Triangle Park, NC.
It has been demonstrated that fetal mice are more sensitive to in utero exposure to the polycyclic hydrocarbon, 3-methylcholanthrene (MC) than are adults, and develop a high incidence of lung tumors 12 months after transplacental exposure to MC. We compared the effects of in utero treatment with MC on lung tumor induction in the offspring of intermediately susceptible Balb/c (Bc), resistant C57BL/6 (B6), and reciprocal crosses between the two strains. Pregnant mice were treated with 45 mg/kg of MC on day 17 of gestation and tumor incidence, multiplicity, and tumor size determined in the offspring 14-18 months after birth. Bc, B6Bc, and BcB6 mice exhibited a 100% tumor incidence whereas the resistant B6 mice had an incidence of 5.3%. B6 mice exhibited 1 small nodule after 18 months whereas Bc mice rarely survived beyond 14 months and BcB6 and B6Bc mice survived to approximately 16 months. Bc, B6Bc, and BcB6 mice exhibited significant tumor involvement in the lungs; in many cases multiple tumors coalesced into single large masses with the majority of lesions classified as adenocarcinomas. Counting only lesions that were discrete, individual nodules, tumor multiplicities in Bc, B6Bc, BcB6, and B6 mice were 7.7?2.9, 5.5?3.3, 6.0?3.0, and <0.1, respectively. Similarly, tumor size in Bc, B6Bc, BcB6, and B6 mice was 1.5?0.7, 1.6?0.9, 1.4?0.7, and