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Title: CARCINOGENICITY OF FUMONISIN B1 IN A TWO-YEAR BIOASSAY WITH FISHER 344 RATSAND B6C3F1 MICE

Author
item HOWARD, PAUL - NCTR/FDA, JEFFERSON, AR
item EPPLEY, ROBERT - CFSAN/FDA, WASHINGTON, DC
item STACK, MICHAEL - CFSAN/FDA, WASHINGTON, DC
item WARBRITTON, ALAN - PATHOL ASSOC,JEFFERSON,AR
item Voss, Kenneth
item LORENTZEN, RONALD - PATHOL ASSOC,JEFFERSON,AR
item KOVACH, ROBERT - PATHOL ASSOC,JEFFERSON,AR
item BUCCI, THOMAS - PATHOL ASSOC,JEFFERSON,AR

Submitted to: Symposium Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 9/1/2000
Publication Date: 12/31/2000
Citation: N/A

Interpretive Summary: Fumonisins are mycotoxins produced by common Fusarium molds which grow on corn. Fumonisins are responsible for fatal diseases in farm animals and they cause liver and kidney damage in laboratory animals. There is circumstantial evidence that fumonisins may cause cancer in humans who depend on corn as a dietary staple. To study the cancer causing potential of long-term fumonisin exposure, fumonisin B1, the most commonly found fumonisin, was fed to rats and mice for 2 years. Fumonisin B1 caused increased cancer incidences when fed at 50 ppm or higher. The type of tumors differed by sex and species; kidney tumors were found in male rats and liver tumors in female mice.Thus, this study established that fumonisin B1 causes tumors in rats and mice. The data are important for evaluating the health risks of fumonisin management strategies. Exploiting the different effects seen in rats and mice may be useful in future studies to determine the biochemical mechanism by which fumonisins exert their effects.

Technical Abstract: Fumonisins are mycotoxins produced by Fusarium moniliforme (=F. verticillioides) and other Fusarium found on corn. Some F. verticillioides isolates are rodent carcinogens and are suspected human (esophageal) carcinogens. To study the carcinogenic potential of fumonisins, fumonisin B1 (FB1), the most common fumonisin, was fed to F344/N rats and B6CF1 mice for two years (48/sex/group) at dietary concentrations of: male rats - 0, 5, 15, 50 and 150 ppm; female rats - 0, 5, 15, 50 and 100 ppm; male mice - 0, 15, 15, 80 and 150 ppm; and female mice - 0, 5, 15, 50 and 80 ppm. In rats there were no survival or body weight effects. Renal tubule adenomas were found in 2/48 and 5/48 males fed 50 ppm and 150 ppm, respectively, and renal tubule carcinomas were found in 7/48 males fed 50 ppm and 10/48 males fed 150 ppm. FB1 did not cause tumors in female rats. FB1 had no effect on body weight of mice. Survival of females fed 80 ppm FB1 was reduced. The incidences of liver (hepatocellular) tumors were increased in female mice. Adenomas were found in 16/47 and 31/45 females fed 50 ppm and 80 ppm FB1, respectively, and carcinomas were found in 10/47 females fed 50 ppm and 9/45 females fed 80 ppm FB1. No tumorigenic effects were found in male mice. Although differences in response by sex and target organ were seen, the carcinogenic activity of 50 ppm FB1 was clearly established in two rodent species.