Sex differential and dose dependence of phenobarbital-promoting activity in N-bis(2-hydroxypropyl)nitrosamine-initiated thyroid tumorigenesis in rats.
Studies were made on the dose and sex dependence of thyroid tumor development in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN) followed by exposure to various doses of phenobarbital (PB). A direct dose-response relationship in induction of thyroid tumors was found in both male and female rats. Upon feeding the DHPN-treated rats with basal diet containing 20, 100, 500, and 2500 ppm of PB, the incidences of follicular adenoma were, respectively, 8, 45, 70, and 66% in male rats and 12, 17, 50, and 58% in female rats. Development of papillary adenomas in male rats was observed only at the higher doses of PB, at incidences of 12 and 20% for doses of 500 and 2500 ppm. Follicular carcinoma was also seen at higher doses of PB, at 16 and 12%, respectively, for the 500- and 2500-ppm groups. Neither follicular nor papillary carcinomas were induced in female rats; only a low incidence of papillary adenoma (4%) was observed with a PB concentration as high as 2500 ppm. A single injection of DHPN resulted in production of approximately 1 tumor/female rat and 2.5 tumors/male rat. DHPN combined with posttreatment with PB at doses up to 500 ppm did not increase tumor yield in female rats, whereas a 3-fold increase was observed in male rats for the 500-ppm-treated groups. When PB was increased to 2500 ppm a marked increase (8-fold) in tumor yield in male rats was observed, in contrast to a less than 3-fold increase in similarly treated female rats.
D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013963:Thyroid Hormones / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D009602:Nitrosamines; D013963:Thyroid Hormones; C012457:diisopropanolnitrosamine; D010634:Phenobarbital