Temporal advancement of diethylnitrosamine carcinogenesis in aging mice

Female BALB/c mice were given diethylnitrosamine (DEN) in their drinking water beginning at 2.5, 9.5, and 17 months of age (cumulative dose approximately 300 to 400 mg/kg body weight) or were untreated. Median times of death for the treatment groups were 193, 168, and 125 days, respectively, after cessation of DEN treatment and were significantly different (p less than .01). Induced tumors in the three respective age groups were of squamous forestomach (88, 87, and 84%), vascular tumors of the liver (11, 13, and 16%), and adenomas of the lung (65, 56, and 54%). Controls had no forestomach or liver tumors and relatively low incidences of lung tumors. The fact that aging mice have similar incidences and types of tumors of the same size and in the same tissues, but at an earlier time, shows that (1) DEN is carcinogenic in aging BALB/c mice; (2) age at treatment does not alter the tumor-susceptible tissue nor types of tumors after DEN treatment; (3) tumor incidences are not affected by age at time of treatment; (4) mice die earlier with induced tumors with increasing age at time of treatment; (5) age-matched non-DEN-treated mice die from different diseases (leukemias) than do DEN-treated mice (stomach and liver tumors). These observations may be related, in part, to an identified age-dependent decrease in immunocompetency or to other age-related changes, such as vascular or hormonal, which could explain temporal advancement in the tumorigenic process.