These mutations were reduced by treatment of mice with diallyl sulfone before VC and coincided with a reduction in the number of lung tumors with Kras2 mutations.
Moreover, a major lung tumor susceptibility locus, the Pas1 (Pulmonary adenoma susceptibility 1), was found to colocalize with Kras2 on distal chromosome 6 on linkage analysis.
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.
Primer extension assays with purified BALB/cJ and A/J proteins in vitro demonstrate that both forms of Pol iota are active but that they may differ in substrate discrimination, which may affect the formation of Kras2 mutations in mouse lung tumors.
Previous studies showed that significant differences in mutation frequency of the human c-Ha-ras transgene between vinyl carbamate (VC)- and ethyl carbamate (urethane)-induced lung tumors were observed in rasH2 mice.
Aberrant expression of cyclin D1 in pulmonary proliferative lesions induced by high doses of urethane in transgenic mice carrying the human prototype c-H-ras gene.
Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.
Pulmonary adenoma susceptibility 1 (Pas1), the major locus affecting inherited predisposition to lung tumor development in mice, maps near the Kras2 gene.
Carcinogen dose-dependent variation in the transgene mutation spectrum in urethane-induced lung tumors in transgenic mice carrying the human prototype c-Ha-ras gene.
Carcinogen dose-dependent variation in the transgene mutation spectrum in urethane-induced lung tumors in transgenic mice carrying the human prototype c-Ha-ras gene.
In contrast, 10 tumors had substantially elevated levels of p21ras products with respect to the adjacent normal lung tissues and with respect to the other lung tumors.