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

Abstract

Fumonisin B1(FB1) is a fungal metabolite of Fusarium verticillioides (= F. moniliforme), a fungus that grows on many crops worldwide. Previous studies demonstrated that male BD IX rats consuming diets containing 50 ppm fumonisin B1 developed hepatocellular carcinomas. In our recent studies, diets containing FB1 at 50 ppm or higher concentrations induced renal tubule carcinomas in male F344/N/Nctr BR rats and hepatocellular carcinomas in female B6C3F1/Nctr BR mice. The carcinogenicity of FB1 in rats and mice is not due to DNA damage, as several laboratories have demonstrated that FB1 is not a genotoxin. FB1 induces apoptosis in cells in vitro. Including FB1 in the diets of rats results in increased hepatocellular and renal tubule epithelial cell apoptosis. In studies with F344/N/Nctr BR rats consuming diets containing up to 484 ppm FB1 for 28 days, female rats demonstrated more sensitivity than male rats in the induction of hepatocellular apoptosis and mitosis. Conversely, induction of renal tubule apoptosis and regeneration were more pronounced in male than in female rats. Induction of renal tubule apoptosis and hyperplasia correlated with the incidence of renal tubule carcinomas that developed in the 2-year feeding study with FB1 in the F344/N/Nctr BR rats. The data are consistent with the hypothesis that the induction of renal tubule carcinomas in male rats could be partly due to the continuous compensatory regeneration of renal tubule epithelial cells in response to the induction of apoptosis by fumonisin B1.

Complex etiology and pathology of mycotoxic nephropathy in South African pigs

“…FB 1 (Gelderblom et al 1992;Howard et al 2001) and PA (Dickens and Jones 1961;Palmgren and Ciegler 1983) were also found to be carcinogenic mycotoxins and may interact with OTA, which is a potent carcinogen. Moreover, FB 1 was found to have a pronounced nephrotoxic effect on animal kidneys Bucci et al 1998), which can be additive to the nephrotoxic effect of OTA.…”

The Y123H substitution perturbs FvCYP51B function and confers prochloraz resistance in laboratory mutants of Fusarium verticillioides

“…Toxins produced by F . verticillioides such as fumonisin B 1 can be detected in plant tissues (especially in kernels) with and without symptoms, and are harmful to humans and animals (Marasas et al ., ; Howard et al ., ). This fungal pathogen primarily penetrates seeds and then moves to the root, mesocotyl and crown, and ultimately to the kernels (Munkvold et al ., ; Murillo‐Williams & Munkvold, ).…”

“…Fusarium verticillioides (teleomorph Gibberella fujikuroi (synonym, Gibberella fujikuroi)) is a widely distributed plant pathogen that causes many important diseases of corn including seedling blight, root rot, stalk rot, and kernel or ear rot (Foley, 1962;Kommedahl & Windels, 1981). Toxins produced by F. verticillioides such as fumonisin B 1 can be detected in plant tissues (especially in kernels) with and without symptoms, and are harmful to humans and animals (Marasas et al, 1984;Howard et al, 2001). This fungal pathogen primarily penetrates seeds and then moves to the root, mesocotyl and crown, and ultimately to the kernels (Munkvold et al, 1997;Murillo-Williams & Munkvold, 2008).…”

Porcine/Chicken or Human Nephropathy as the Result of Joint Mycotoxins Interaction

“…FB1 [114,115] and PA [73,74] were also found to be carcinogenic mycotoxins and may interact in this dimension with OTA, which is also proven carcinogen [76,116,117,118]. Moreover, FB1 was found to have a pronounced nephrotoxic effect on animal kidneys [61,119], which can be additive to nephrotoxic effect of OTA.…”