Sex differential and dose dependence of phenobarbital-promoting activity in N-bis(2-hydroxypropyl)nitrosamine-initiated thyroid tumorigenesis in rats.

Abstract

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.

• Authors: Y Hiasa, Y Kitahori, N Konishi, T Shimoyama, J C Lin
• Journal: Cancer research (Cancer Res) Vol. 45 Issue 9 Pg. 4087-90 (Sep 1985) ISSN: 0008-5472 [Print] United States
• PMID: 4028001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Nitrosamines
• Thyroid Hormones
• diisopropanolnitrosamine
• Phenobarbital

Topics

• Animals
• Carcinogens
• Cocarcinogenesis
• Dose-Response Relationship, Drug
• Female
• Male
• Nitrosamines (toxicity)
• Phenobarbital (toxicity)
• Rats
• Rats, Inbred Strains
• Sex Factors
• Thyroid Hormones (metabolism)
• Thyroid Neoplasms (chemically induced, pathology)