Journal Article

The promotion effect of anorectic drugs on aflatoxin B<sub>1</sub>-induced hepatic preneoplastic foci

Xu Lin, David A. Levitsky, John M. King and T. Colin Campbell

in Carcinogenesis

Volume 20, issue 9, pages 1793-1799
Published in print September 1999 | ISSN: 0143-3334
Published online September 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.9.1793
The promotion effect of anorectic drugs on aflatoxin B1-induced hepatic preneoplastic foci

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The ability of three extensively used anorectic drugs, namely fenfluramine (FN), fluoxetine (FX) and amphetamine (AM), to alter the development of aflatoxin B1 (AFB1)-induced γ-glutamyl-positive (GGT+) preneoplastic liver foci was investigated in 135 male weanling F344 rats. Following AFB1 administration, 15 rats were killed, while the rest were divided into four groups and fed diets containing either FN, FX, AM or control diet, with half of the animals in each group subsequently being killed at 4 weeks and half at 10 weeks. All three anorectic drugs as expected suppressed initial food intake, growth rate, body weight gain and food efficiency. They also tended to suppress body fat mass and to decrease plasma levels of T3 and T4. FN significantly (P < 0.05) increased GGT+ foci number/cm2 and number/cm3, while FX significantly increased GGT+ foci number/cm2 and the volume fraction of foci. Histopathological staining also revealed that FN- and FX-treated animals had more serious morphological alterations in their liver tissue. In contrast, foci development was, if anything, suppressed by AM feeding. These results indicate that serotoninergic drugs (FN and FX), as opposed to dopaminergic drugs (AM), may have tumor promoter activity, at least for liver tissue.

Keywords: AFB1, aflatoxin B1; AM, amphetamine; BAT, brown adipose tissue; DIT, diet-induced thermogenesis; FN, fenfluramine; FX, fluoxetine; GGT, γ-glutamyltranspeptidase; GGT+, γ-glutamyl-positive; H&E, hematoxylin and eosin; T3, triiodothryonine; T4, thyroxine.

Journal Article.  5635 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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