Absence of a synergistic effect between fumonisin B1 and N-nitrosomethylbenzylamine in the induction of oesophageal papillomas in the rat.
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.
Wild
C P
CP
Molecular Epidemiology Unit, Research School of Medicine, University of Leeds, United Kingdom.
Castegnaro
M
M
Ohgaki
H
H
Garren
L
L
Galendo
D
D
Miller
J D
JD
D000818:Animals; D002264:Carboxylic Acids / Q000009:adverse effects / Q000494:pharmacology*; D002273:Carcinogens / Q000009:adverse effects / Q000494:pharmacology*; D003043:Cocarcinogenesis; D004128:Dimethylnitrosamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D037341:Fumonisins; D007263:Infusions, Parenteral; D008297:Male; D010212:Papilloma / Q000139:chemically induced*; D051381:Rats
D002264:Carboxylic Acids; D002273:Carcinogens; D037341:Fumonisins; C056933:fumonisin B1; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine