fumonisin-b1 and Cocarcinogenesis

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.

Topics: Aflatoxin B1; Algorithms; Animals; Body Weight; Carboxylic Acids; Carcinogens, Environmental; Cocarcinogenesis; Disease Models, Animal; Fumonisins; Glutathione S-Transferase pi; Glutathione Transferase; Immunohistochemistry; Isoenzymes; Liver; Organ Size; Rats; Staining and Labeling; Time Factors

Fumonisins and N-nitrosamines (NNO) are suggested risk factors in the development of human oesophageal cancer; exposure to both occurs in high risk populations in Africa and People's Republic of China. The hypothesis that the two would interact in oesophageal carcinogenesis was therefore tested by treating male rats with the known oesophageal carcinogen N-methylbenzylnitrosamine (NMBA), and fumonisin B1 (FB1). The treatment groups were: Group 1, NMBA (2.5 mg/kg) intraperitoneally twice per week from week 2 to 4 inclusive; Group 2, as for group 1 but in addition FB1 (5 mg/kg) daily from weeks 1 to 5 inclusive by gavage; Group 3, FB1 (5 mg/kg) alone daily from weeks 1 to 5 inclusive by gavage, and Group 4, vehicle treatment from week 1 to 5 inclusive. Two of 12 animals in group 1 developed oesophageal papillomas and a further two had oesophageal dysplasia. Data were similar in group 2, animals receiving both NMBA and FB1, with one of 12 animals having papillomas and three of 12 with dysplasia. Sphingolipid biosynthesis was affected in the kidney and slightly in the liver after fumonisin treatment but not in the oesophagus or lung as determined by sphinganine:sphingosine ratios in urine and tissues. These data show that there is no synergistic interaction between NMBA and FB1 in the rat oesophagus when the two compounds are administered together. It is nevertheless important to examine other experimental models and treatment protocols which may be more relevant to the human situation and also to pursue epidemiological investigations of the role of fumonisins in oesophageal cancer.

Topics: Animals; Carboxylic Acids; Carcinogens; Cocarcinogenesis; Dimethylnitrosamine; Drug Synergism; Esophageal Neoplasms; Fumonisins; Infusions, Parenteral; Male; Papilloma; Rats