Interaction of fumonisin B(1) and aflatoxin B(1) in a short-term carcinogenesis model in rat liver.
The co-existence of the fumonisin and aflatoxin mycotoxins in corn merited studies to investigate their possible synergistic toxicological and carcinogenic effects. When utilising a short-term carcinogenesis model in rat liver, both the compounds exhibited slow cancer initiating potency as monitored by the induction of foci and nodules stained positively for the placental form of gluthatione-S-transferase (GSTP(+)). However, when rats were treated in a sequential manner with AFB(1) and FB(1) the number and size of GSTP(+) lesions significantly increased as compared to the separate treatments. Histopathological analyses indicated that the individual treatments showed far less toxic effects, including occasional hepatocytes with dysplastic nuclei, oval cell proliferation and, in the case of FB(1), a few apoptotic bodies in the central vein regions. The sequential treatment regimen induced numerous foci and dysplastic hepatocyte nodules, and with oval cells extending from the periportal regions into the centrilobular regions. This would imply that, in addition to the cancer promoting activity of FB(1) of AFB(1)-initiated hepatocytes, the AFB(1) pre-treatment enhanced the FB(1) initiating potency, presumably by rendering the liver more susceptible to the toxic effects of FB(1). The co-occurrence of AFB(1) and FB(1) in corn consumed as a staple diet could pose an increased risk and should be included in establishing risk assessment parameters in humans.
Gelderblom
W C A
WC
PROMEC Unit, Medical Research Council, P.O. Box 19070, 7505, Tygerberg, South Africa. wentzel.gelderblom@mrc.ac.za
Marasas
W F O
WF
Lebepe-Mazur
S
S
Swanevelder
S
S
Vessey
C J
CJ
Hall
P de la M
Pde L
D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000009:adverse effects*; D000465:Algorithms; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D002274:Carcinogens, Environmental / Q000009:adverse effects*; D003043:Cocarcinogenesis; D004195:Disease Models, Animal; D037341:Fumonisins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013194:Staining and Labeling; D013997:Time Factors
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; D007527:Isoenzymes; C056933:fumonisin B1; D016604:Aflatoxin B1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496558:Gstp1 protein, rat