Induction of lung carcinogenesis in AKR-mice by N-nitrosodiethylamine/phenobarbitone, associated with high expression of c-myc and c-jun oncoproteins

Lung carcinogenesis was induced in AKR mice using N-nitrosodiethylamine (NDEA). Tumors were detected in 46.8% of mice provided with 100 ppm NDEA in drinking water. The incidence of tumors was increased to 64.2% when the same carcinogenesis was promoted by phenobarbitone (PB). Lung tumor bearing mice showed no tumors in other organs. Characteristic features of these lung tumors are: (i) appearance of tumors within a short period of time i.e. less than 75 days; (ii) no increase in the number and size of tumors with the increase in dose and duration of treatment of carcinogen; (iii) the same histological type was maintained in more than 80% of tumors. Animals that received treatment for 75-125 days showed no significant advancement in the stage of carcinogenesis in comparison to the 50-75 days treatment period. Moreover, mice which received treatment for 125-150 days, did not have any neoplastic lesions in lungs, but they consisted of liver tumors generally. Expression of oncoproteins, c-myc and c-jun, was detected in all lung tumors but the expression of c-myc protein was more than that of c-jun and both of these oncoproteins were enhanced by the promoter, PB. Highest level of expression of c-myc and c-jun was detected within the period of 50-75 days, whereafter it was decreased significantly within the period of 75-125 days and 125-150 days of treatment. Thus, the results indicate that c-myc/c-jun might be involved in the development of lung cancer in AKR mice, but may not have any role in the maintenance of the malignant phenotype of lungs. (C) 1997 Elsevier Science Ireland Ltd.