Pulmonary Toxicity of Inhaled Diesel Exhaust and Carbon Black in Chronically Exposed Rats. Part 3. Examination of Possible Target Genes

摘要

Mutations were analyzed in the K-ras protooncogene and the p53 tumor suppressor gene from lung tumors induced in rats by prolonged inhalation of high concentrations of diesel engine exhaust (which had adsorbed mutagenic organic compounds) or carbon black particles (which were relatively free of mutagens). K-ras mutations were identified in 3 of 50 tumors, but no p53 mutations were detected. No pattern of mutation or protein immunoreactivity was detected that would suggest a mechanisms of carcinogenicity differentiated between diesel exhaust and carbon black. Therefore, these findings do not support or negate a role for the mutagenic organic constituents of diesel exhaust. However, inactivation of p53 may have a role in the induction of lung tumors with a squamous cell carcinoma component.