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.
Giri
R K
RK
Molecular Biology Division, Institute of Life Sciences, Sahid Nagar, Bhubaneswar, India.
Baral
R N
RN
Das
B R
BR
D000818:Animals; D002273:Carcinogens; D004052:Diethylnitrosamine; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009363:Neoplasm Proteins / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010634:Phenobarbital; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
D002273:Carcinogens; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D004052:Diethylnitrosamine; D010634:Phenobarbital