The effect of age on susceptibility of rats to carcinogenesis by two nitrosamines.
The carcinogenic effects of identical doses of two carcinogenic nitrosamines each given to young (8-week-old) and old (54- or 65-week-old) F344 rats were compared. The two compounds were nitrosomorpholine, which was given in drinking water to females, and nitrosobis(2-oxopropyl)amine (BOP), which was given to males by gavage in oil. In both old (54 weeks) and young rats nitrosomorpholine at 100 mg/liter induced hepatocellular neoplasms in the liver of almost all rats, but the rate at which the neoplasms killed the animals was much slower in the old than in the young rats, and by this measure of potency the old rats given 100 mg/liter resembled young rats given 40 mg/liter. BOP administered at two dose rates, 2.5 mg twice a week for 35 weeks, and 6 mg twice a week for 29 weeks, induced neoplasms of the lung and of follicular cells in the thyroid and transitional cell neoplasms of the bladder and kidney pelvis in almost all animals when treatment began at 8 weeks, but many fewer, or none, of these neoplasms in male rats whose treatment began at 65 weeks. Instead, the old male rats developed hepatocellular neoplasms in the liver, none of which were seen in the young rats treated with BOP. There was no significant difference in mortality rate between young and old rats which would account for these differences in BOP-treated rats.
D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced
D009602:Nitrosamines; C002741:N-nitrosomorpholine; C013622:nitrosobis(2-oxopropyl)amine