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Cell kinetics in mouse lung following administration of carcinogens and butylated hydroxytoluene

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)
A series of experiments is described which was designed to test the hypothesis that, in mouse lung, enhancement of tumor development could occur independently of overall alveolar cell hyperplasia. Male A/J mice were given 1000 mg/kg of urethane or 10 mg/kg of 3-methylcholanthrene (MCA). Alveolar cells were labeled through continuous infusion of (TH)thymidine for 6 weeks after administration of the carcinogen. Urethane produced a significant hyperplasia of the type II alveolar cell population, whereas MCA had no such effect. Five repeated injections of 300 mg/kg of butylated hydroxytoluene (BHT), a procedure known to enhance lung tumor development, produced cell hyperplasia only during the first 2 weeks; later the mice became resistant to the action of BHT. In animals treated with piperonyl butoxide prior to BHT, cell proliferation was abolished. BHT still had a small but significant enhancing effect on tumor development. However, this effect was dwarfed by the observation that piperonyl butoxide alone greatly inhibited tumor development. The data do not allow exclusion of alveolar cell hyperplasia as a mechanism in BHT-mediated enhancement of mouse lung tumor development. 19 references, 4 figures, 3 tables.
Research Organization:
Oak Ridge National Lab., TN
DOE Contract Number:
AC05-84OR21400
OSTI ID:
6228412
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 78; ISSN TXAPA
Country of Publication:
United States
Language:
English