The cancer-promoting potential of fumonisin B1 in rat liver using diethylnitrosamine as a cancer initiator.
The cancer-promoting potential of fumonisin B1 (FB1) was investigated by feeding different dietary levels (10, 50, 100, 250, 500 mg FB1/kg) to diethynitrosamine (DEN)-initiated rats for 21 days. Dietary levels containing 50 mg FB1/kg and higher, markedly increased the number and size of the placental form of glutathione-S-transferase-positive (GSTP+) foci in the liver of the rats. The cancer-promoting activity of FB1 was associated with an inhibitory effect on partial hepatectomy (PH)-induced regenerative hepatocyte proliferation, as the incorporation of 3H-labelled thymidine was significantly (P < 0.05) reduced by those FB1-containing diets that exhibited cancer promotion. In vitro studies on the mitogenic activity of epidermal growth factor (EGF) in primary rat hepatocytes further supported the in vivo data in that FB1, similar to other cancer promoters such as phenobarbital and 2-acetylaminofluorene (2-AAF), alters growth stimulatory responses in primary hepatocytes. No significant (P > 0.05) changes in the sphinganine/sphingosine (Sa/So) ratio were observed in the liver of the rats fed the lowest FB1-containing diet (50 mg FB1/kg diet) that effected cancer promotion. The present study indicated that FB1 exhibited cancer-promoting activity in the absence of adverse hepatotoxic effects and at dietary levels that failed to effect cancer initiation.
Gelderblom
W C
WC
Department of Veterinary Pathology, University of Pretoria, South Africa.
Snyman
S D
SD
Lebepe-Mazur
S
S
van der Westhuizen
L
L
Kriek
N P
NP
Marasas
W F
WF
D000818:Animals; D002264:Carboxylic Acids / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D004052:Diethylnitrosamine; D004357:Drug Synergism; D037341:Fumonisins; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009183:Mycotoxins / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; D009183:Mycotoxins; D004052:Diethylnitrosamine; C056933:fumonisin B1; D005982:Glutathione Transferase