This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiasa, Y. Articles by Lin, J.-C. Search for Related Content PubMed PubMed Citation Articles by Hiasa, Y. Articles by Lin, J.-C.

Sex Differential and Dose Dependence of Phenobarbital-promoting Activity in N-Bis(2-hydroxypropyl)nitrosamine-initiated Thyroid Tumorigenesis in Rats¹

First Department of Pathology, Nara Medical University, Kashihara, Nara 634, Japan [Y. H., Y. K., N. K., T. S.], and Lineberger Cancer Research Center, University of North Carolina, Chapel Hill, North Carolina 27514 [J-C. L.]

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 <3-fold increase in similarly treated female rats.

¹ This research was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education of Japan.

² To whom requests for reprints should be addressed.

Received 1/23/84. Revised 5/14/85. Accepted 5/22/85.

This article has been cited by other articles:

				N. Nishimura, J. Yonemoto, Y. Miyabara, M. Sato, and C. Tohyama Rat Thyroid Hyperplasia Induced by Gestational and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Endocrinology, May 1, 2003; 144(5): 2075 - 2083. [Abstract] [Full Text] [PDF]

				S. Johnson, D. McKillop, J. Miller, and I.K. Smith The Effects on Rat Thyroid Function of an Hepatic Microsomal Enzyme Inducer Human and Experimental Toxicology, January 1, 1993; 12(2): 153 - 158. [Abstract] [PDF]

				R. M. McClain The Significance of Hepatic Microsomal Enzyme Induction and Altered Thyroid Function in Rats: Implications for Thyroid Gland Neoplasia Toxicol Pathol, February 1, 1989; 17(2): 294 - 306. [Abstract] [PDF]