The promotion effect of anorectic drugs on aflatoxin B(1)-induced hepatic preneoplastic foci.
The ability of three extensively used anorectic drugs, namely fenfluramine (FN), fluoxetine (FX) and amphetamine (AM), to alter the development of aflatoxin B(1) (AFB(1))-induced gamma-glutamyl-positive (GGT(+)) preneoplastic liver foci was investigated in 135 male weanling F344 rats. Following AFB(1) 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 T(3) and T(4). FN significantly (P < 0.05) increased GGT(+) foci number/cm(2) and number/cm(3), while FX significantly increased GGT(+) foci number/cm(2) 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.
Lin
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Division of Nutritional Sciences and Department of Pathology, Veterinary Medicine College, Cornell University, Ithaca, NY 14853, USA.lin00026@mc.duke.edu
Levitsky
D A
DA
King
J M
JM
Campbell
T C
TC
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000473:pathology; D016604:Aflatoxin B1 / Q000494:pharmacology / Q000633:toxicity*; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D001067:Appetite Depressants / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D001833:Body Temperature Regulation / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D003043:Cocarcinogenesis; D004298:Dopamine / Q000502:physiology; D004357:Drug Synergism; D004435:Eating; D004734:Energy Metabolism; D005277:Fenfluramine / Q000633:toxicity*; D005473:Fluoxetine / Q000633:toxicity*; D006130:Growth Disorders / Q000139:chemically induced; D007037:Hypothyroidism / Q000139:chemically induced; D008107:Liver Diseases / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D015431:Weight Loss / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000032:analysis
D016604:Aflatoxin B1; D000661:Amphetamine; D001067:Appetite Depressants; D015415:Biomarkers; D002273:Carcinogens; D004298:Dopamine; D005277:Fenfluramine; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D005723:gamma-Glutamyltransferase