The objectives of this study were to (i) evaluate benign and malignant lung neoplasms from B6C3F1 mice for mutations in the K-ras gene at codons 12, 13 and 61, (ii) determine if the frequency and spectra of K-ras mutations were unique for ozone-induced lung neoplasms, (iii) determine if specific K-ras mutations were associated with the size and morphological patterns of lung neoplasms or ozone exposure concentrations and (iv) screen lung neoplasms by immunohistochemical methods for the p53 protein.
Mutations of the Ki-ras protooncogene in 3-methylcholanthrene and urethan-induced and butylated hydroxytoluene-promoted lung tumors of strain A/J and SWR mice.
High frequency of codon 61 K-ras A-->T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene.
BHT, a lung tumor promoter in adult mice, had no statistically significant effects on either tumor incidence, tumor multiplicity or the mutational spectrum produced in the Ki-ras gene by in utero MC treatment.
Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras.
Decrease in K-ras p21 and increase in Raf1 and activated Erk 1 and 2 in murine lung tumors initiated by N-nitrosodimethylamine and promoted by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Map kinase activation correlates with K-ras mutation and loss of heterozygosity on chromosome 6 in alveolar bronchiolar carcinomas from B6C3F1 mice exposed to vanadium pentoxide for 2 years.
The incidence of KRAS2 mutations in human compared to mouse lung tumors differed significantly, as did the incidence of Hras and p53 gene mutations in human compared to mouse liver tumors.
We propose that the Pas1 modifier effect is due to Kras2, and that a sensitive balance between the expression levels of wild-type and mutant alleles determines lung tumor susceptibility.
K-ras mutations in lung tumors and tumors from other organs are consistent with a common mechanism of ethylene oxide tumorigenesis in the B6C3F1 mouse.
Enhancement of lung carcinogenesis initiated with 4-(N-hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone by Ogg1 gene deficiency in female, but not male, mice.