Journal article

Publication year: 1990

Pages: 3701-3708

Journal: Cancer Research

Volume number: 50

Issue number: 12

ISSN: 0008-5472

eISSN: 1538-7445

Publisher: American Association for Cancer Research

Abstract: 
The involvement of tumor promotion in the hepatocarcinogenic action of peroxisome proliferators has not been generally accepted. We studied the effect of nafenopin (NAF) as a model compound in a two-stage initiation-promotion protocol. Carcinogenesis was initiated by a single dose of aflatoxin B1 (AFB1) in female (AFB1, 5 mg/kg) and male (AFB1, 2 mg/kg) Wistar rats. After recovery NAF was fed via the diet, providing a daily dose of 100 mg/kg body weight. Phenobarbital (PB (50 mg/kg body weight) was fed to female rats as a positive control. The following results were obtained. (a) At weeks 40, 55, 59, and 70, significantly more and larger liver tumors were present in AFB1-NAF-treated rats than in rats receiving either compound alone, and the effect of the combined treatment was clearly more than additive, in three independent experiments including both sexes. This suggests tumor promotion by NAF. Male rats responded more strongly than females. Similarly, PB enhanced the yield of liver tumors. Histologically, tumors were hepatocellular adenoma or carcinoma. In group AFB1-PB the majority consisted of eosinophilic and glycogen-storing cells. However, adenoma and carcinoma of groups AFB1-NAF and O-NAF consisted of weakly basophilic cells. (b) phenotypically altered foci were evaluated in hematoxylin- and eosin-stained liver sections from the female rats. NAF treatment after AFB1 had little effect on number and size of eosinophilic-clear cell foci and decreased the number of tigroid foci. However, it led to a dramatic increase (20-fold after 70 weeks of NAF treatment) in number and size of foci of a special phenotype that was extremely rare after AFB1 alone and virtually absent in group AFB1-PB. Hepatocytes in these foci are characterized by weak diffuse basophilia and some eosinophilia, similar to the phenotype in adenoma and carcinoma, and by absence of .gamma.-glutamyltranspeptidase (GGT) expression. Based on these findings, we propose the hypothesis tht NAF promotes the development of liver tumors via a mechanism involving amplification of a specific subtype of altered hepatic foci.

Harvard Citation style: KRAUPPGRASL, B., HUBER, W., PUTZ, B., GERBRACHT, U. and SCHULTEHERMANN, R. (1990) TUMOR PROMOTION BY THE PEROXISOME PROLIFERATOR NAFENOPIN INVOLVING A SPECIFIC SUBTYPE OF ALTERED FOCI IN RAT-LIVER, Cancer Research, 50(12), pp. 3701-3708

APA Citation style: KRAUPPGRASL, B., HUBER, W., PUTZ, B., GERBRACHT, U., & SCHULTEHERMANN, R. (1990). TUMOR PROMOTION BY THE PEROXISOME PROLIFERATOR NAFENOPIN INVOLVING A SPECIFIC SUBTYPE OF ALTERED FOCI IN RAT-LIVER. Cancer Research. 50(12), 3701-3708.