Evaluation of genetic alterations in cancer-related genes in lung and brain tumors from B6C3F1 mice exposed to 1,3-butadiene or chloroprene.
1,3-Butadiene and chloroprene are multisite carcinogens in B6C3F1 mice with the strongest tumor response being the induction of lung neoplasms in females. Incidence of brain tumors in mice exposed to 1,3-butadiene was equivocal. This article reviews the efforts of our laboratory and others to uncover the mechanisms of butadiene and chloroprene induced lung and brain tumor responses in the B6C3F1 mouse. The formation of lung tumors by these chemicals involved mutations in the K-ras cancer gene and loss of heterozygosity in the region of K-ras on distal chromosome 6, while alterations in p53 and p16 were implicated in brain tumorigenesis.
Ton
Thai-Vu
TV
Environmental Toxicology Program and Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, MD B3-08, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. ton@niehs.nih.gov
Hong
Hue-Hua
HH
Devereux
Theodora R
TR
Melnick
Ronald L
RL
Sills
Robert C
RC
Kim
Yongbaek
Y
D000483:Alleles; D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced / Q000235:genetics*; D002070:Butadienes / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002737:Chloroprene / Q000008:administration & dosage / Q000633:toxicity*; D033481:Chromosomes, Mammalian / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D019570:Inhalation Exposure; D019656:Loss of Heterozygosity / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects*
D002070:Butadienes; D002273:Carcinogens; D018736:DNA Adducts; D002737:Chloroprene; C031763:1,3-butadiene