Cancer initiating properties of fumonisin B1 in a short-term rat liver carcinogenesis assay.
The nature of cancer initiation by fumonisin B(1) (FB(1)) was investigated in rat liver by monitoring the effect of phenobarbital (PB) as cancer promoter and evaluating the involvement of spontaneously initiated cells. A PB promoting regimen (0.05% in the diet) stimulated the outgrowth of FB(1)-induced placental glutathione S-transferase (GSTP) positive initiated hepatocytes. Reversion of the FB(1)-induced GSTP(+) foci was noticed in the absence of a promoting regimen. Younger rats were shown to be more sensitive to the induction of GSTP(+) foci by FB(1). Cancer initiation by FB(1) was associated with a hepatotoxic effect, which was less pronounced in older rats presumably due to a reduced intake. A specific role of spontaneously initiated cells and their promotion by FB(1) into the development of eosinophilic clear cell foci could not be established under the present experimental conditions. The ability of different stimuli to selectively promote the outgrowth of FB(1) initiated cells further verifies the cancer initiating potency of this apparent non-genotoxic mycotoxin. The underlying mechanism(s) involved in the genesis of the initiated hepatocytes is not known at present.
Gelderblom
W C A
WC
Program on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa. wentzel.gelderblom@mrc.ac.za
Marasas
W F O
WF
Lebepe-Mazur
S
S
Swanevelder
S
S
Abel
S
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects; D037341:Fumonisins / Q000633:toxicity*; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D015430:Weight Gain / Q000187:drug effects
D002273:Carcinogens; D037341:Fumonisins; C056933:fumonisin B1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496558:Gstp1 protein, rat; D010634:Phenobarbital