Strain-specific induction of murine lung tumors following in utero exposure to 3-methylcholanthrene.
Fetal mice are more sensitive to chemical carcinogens than are adults. We previously demonstrated that resistant offspring of a DBA/2 x (C57BL/6 x DBA2) backcross exhibited a high incidence of lung tumors 12-13 mo after transplacental exposure to 3-methylcholanthrene (MC). We compared the effects of in utero treatment with MC on lung tumor incidence in the offspring of intermediately susceptible BALB/c (C), resistant C57BL/6 (B6), and reciprocal crosses between these strains. Pregnant mice were treated with 45 mg/kg of MC on day 17 of gestation and tumor incidence, multiplicity, and the Ki-ras mutational spectrum determined in the offspring 12-18 mo after birth. Tumor incidences in C mice and reciprocal crosses were 86% and 100%, respectively, while B6 mice demonstrated resistance to tumorigenesis, with a tumor incidence of 11%. Tumor multiplicities in C, B6C, CB6, and B6 mice were 3.3 +/- 3.2, 5.8 +/- 3.2, 5.0 +/- 2.7, and <0.1, respectively. Ki-ras mutations, which occurred chiefly in the K(s) allele (96%), were found in 79-81% of reciprocally crossed F1 mice, 64% of C mice, and 50% of B6 mice, with the Val(12), Asp(12), and Arg(13) mutations associated with more aggressive tumors. A subset of these mice was used to demonstrate the utility of computer tomography (CT) for the visualization and measurement of lung tumors in the submillimeter range in vivo. Based on known genetic differences in murine strains for lung cancer, our results suggest the presence of a previously unidentified genetic factor(s) which appears to specifically influence lung tumorigenesis following exposure to carcinogens during fetal development.
Jennings-Gee
Jamie E
JE
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Moore
Joseph E
JE
Xu
Mian
M
Dance
Stephanie T
ST
Kock
Nancy D
ND
McCoy
Thomas P
TP
Carr
J Jeffrey
JJ
Miller
Mark Steven
MS
D000818:Animals; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D011905:Genes, ras / Q000235:genetics; D007178:Inbreeding; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000235:genetics*; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D049188:Prenatal Injuries / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014599:Uterus
D008748:Methylcholanthrene