Enhancement of lung tumor formation in mice by dietary butylated hydroxytoluene: dose-time relationships and cell kinetics.
Strain A/J mice given injections of 1,000 mg urethan/kg and fed for 12 weeks a diet containing 0.75% of butylated hydroxytoluene (BHT) had significantly more tumors per lung 4 or 9 months later than animals given urethan and fed a control diet. A 2-week exposure to dietary BHT (0.75%) was sufficient to significantly enhance tumor development, and the lowest effective BHT concentration was 0.1%, fed for 8 weeks. Tumor development was also enhanced in animals treated once with 3-methylcholanthrene, benzo[a]pyrene, or N-nitrosodimethylamine and, beginning 24 hours later, fed BHT for 8 weeks. Cell kinetic studies showed that BHT given in the diet produced increased proliferation of type II alveolar cells during the first 2 weeks and that initial cell proliferation was delayed in urethan-treated animals.
D000818:Animals; D001345:Autoradiography; D001835:Body Weight; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003043:Cocarcinogenesis; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D013997:Time Factors; D014520:Urethane / Q000633:toxicity*
D002084:Butylated Hydroxytoluene; D014520:Urethane