Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

Abstract

Fumonisin B1 (FB1) is a mycotoxin isolated from Fusarium fungi that contaminate crops worldwide. A previous study demonstrated that FB1 promoted preneoplastic foci in initiated rats and induced hepatocellular carcinomas in BD IX rats at 50 parts per million (ppm), but fundamental dose-response data were not available to assist in setting regulatory guidelines for this mycotoxin. To provide this information, female and male F344/N/Nctr BR rats and B6C3F1 Nctr BR mice were fed for two years a powdered NIH-31 diet containing the following concentrations of FB1: female rats, 0, 5, 15, 50, and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not tumorigenic in female F344 rats with doses as high as 100 ppm. Including FB1 in the diets of male rats induced renal tubule adenomas and carcinomas in 0/48, 0/40, 9/48, and 15/48 rats at 0, 5, 15, 50, and 150 ppm, respectively. Including up to 150 ppm FB1 in the diet of male mice did not affect tumor incidence. Hepatocellular adenomas and carcinomas were induced by FB1 in the female mice, occurring in 5/47, 3/48, 1/48, 19/47, and 39/45 female mice that consumed diets containing 0, 5, 15, 50, and 80 ppm FB1, respectively. This study demonstrates that FB1 is a rodent carcinogen that induces renal tubule tumors in male F344 rats and hepatic tumors in female B6C3F1 mice.

Fumonisin Production in the Maize Pathogen Fusarium verticillioides: Genetic Basis of Naturally Occurring Chemical Variation

“…Fumonisins are polyketide mycotoxins that can accumulate in maize and can cause animal health problems, including cancer and neural tube defects in laboratory rodents (1,2). Consumption of fumonisin-contaminated maize has also been epidemiologically correlated with human esophageal cancer and neural tube defects in some regions of the world (3,4).…”

The Fusarium verticillioides FUM Gene Cluster Encodes a Zn(II)2Cys6 Protein That Affects FUM Gene Expression and Fumonisin Production

“…On some occasions, this fungus can synthesize the fumonisin family of mycotoxins, which, after ingestion, have been associated with a number of animal diseases, including cancer (15), and have been epidemiologically associated with human esophageal cancer in some regions of the world (23). Of recent concern are findings that fumonisins can disrupt neural tube development in rodents and, based on human epidemiological surveys, may increase the risks of human neural tube defects (24).…”

Mycotoxin Fumonisin B 1 Increases Intestinal Colonization by Pathogenic Escherichia coli in Pigs

“…It induces leukoencephalomalacia in horses, pulmonary edema in pigs, and nephrotoxicity in rats, rabbits, lambs, and calves (3,14,21,22,32,54). In all species studied, both acute and chronic exposure to FB 1 are associated with alteration of sphingolipid metabolism and hepatotoxicity (9,20,21,26,44,46,48).…”