Fumonisin B 1 Carcinogenicity in a Two-Year Feeding Study Using F344 Rats and B6C3F 1 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.

Compensatory regeneration as a mechanism for renal tubule carcinogenesis of fumonisin B1 in the F344/N/Nctr BR rat.

“…The incidence of tumors in male and female F344 rats treated for up to 2 years with FB 1 has been reported (28,33). No liver tumors were detected in the male and female F344 rats in the 2-year study; however, renal tubule adenomas and carcinomas were induced in male rats fed diets containing 50 and 150 ppm FB 1 .…”

“…These doses did not induce formation of hepatic tumors in F344/N/Nctr BR rats (28,33). Consequently, a clear role for hepatocellular apoptosis and proliferation in rat liver tumor development cannot be determined from these studies.…”

“…In the 2-year tumor study where FB 1 was fed to male and female F344/N/Nctr BR rats (28,33), relative liver weights in the male rats were reduced in a dose-dependent manner at all FB 1 doses, whereas relative liver weights in the female rats were not affected by dietary FB 1 (Figure 8). These doses did not induce formation of hepatic tumors in F344/N/Nctr BR rats (28,33).…”

“…Inclusion of FB 1 in the diet of rats for 2 years resulted in formation of renal tubule epithelial cell adenomas and carcinomas in 19 and 31% of male rats fed 50 and 150 ppm, respectively (28,33). The FB 1 -dependent increase in renal tumors was accompanied by an increased incidence of renal tubule hyperplasia in 29 and 17% of male rats fed 50 and 150 ppm FB 1 , respectively (28).…”

“…Inclusion of FB 1 in the diets of F344/N/Nctr BR rats for 2 years resulted in the formation of renal tubule adenomas and carcinomas in male but not in female rats (28,33). We examined kidneys and livers of rats fed diets containing up to 484 ppm FB 1 for 28 days to determine whether the presence of apoptosis and proliferation correlated with the incidence of renal tubule epithelial cells tumors by FB 1 in the 2-year feeding study.…”