Skip to main content
ARS Home » Research » Publications at this Location » Publication #117596


item Carlson, David
item Williams, David
item Spitsbergen, Jan
item Ross, P Frank
item Bacon, Charles
item Meredith, Filmore
item Riley, Ronald

Submitted to: Journal of Toxicology and Applied Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2000
Publication Date: 3/1/2001
Citation: N/A

Interpretive Summary: Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are toxic chemicals produced by molds that are found on corn. Studies with rodents show that FB1 and AFB1 cause cancer in liver. AFB1 is a known liver carcinogen in humans and there is some evidence of an association between FB1 and human cancer. A study was conducted using rainbow trout, an animal with ver low spontaneous tumor incidence, and an accepted model for studying the cancer causing potential of chemicals. Combinations of FB1, AFB1, and another known carcinogen, N-methyl-N'-nitro-nitrosoguanidine (MNNG), were used. In the trout model FB1 was not a complete carcinogen. However, FB1 was shown to enhance (promote) the liver carcinogenicity of AFB1 and MNNG. Surprisingly, FB1 caused a decrease in the number of tumors in kidney and stomach of trout exposed to MNNG. The increased tumors in liver were associated with changes in the amount of a class of fats called sphingolipids. These findings have important implication sfor food safety because FB1 and AFB1 co-occur on low quality corn that is consumed by humans in Africa, China and Central America. In the USA, low quality corn is not used for human consumption.

Technical Abstract: Laboratory studies have described the carcinogenicity of FB1 in rodents and epidemiological evidence suggests an association between fumonisin B1 (FB1) (a mycotoxin produced by Fusarium moniliforme=F. verticillioides) and esophageal cancer in humans. This study was designed to reveal in rainbow trout, a species with very low spontaneous tumor incidence, if FB1 was (i) a complete carcinogen in the absence of an initiator; (ii) a co-carcinogen with aflatoxin B1(AFB1); (iii) a promoter of liver tumors in AFB1 initiated fish; and, (iv) a promoter of liver, kidney, stomach, or swim bladder tumors in fish initiated with N-methyl-N'-nitro- nitrosoguanidine (MNNG). FB-1 was not a complete carcinogen in trout. No tumors were observed in any tissues of fish fed diets containing 0, 5, 25 or 100ppm FB1 for 34 weeks in the absence of a known initiator. FB1 promoted AFB1 initiated liver tumors in fish fed 25ppm FB1 for 42 weeks. In nMNNG initiated fish, liver tumors were promoted in 100ppm FB1 treatments, but FB1 did not promote tumors in any other tissues. Tumor incidences decreased in kidney and stomach in 100ppm FB1 treatments of MNNG initiated trout. A one-week pre-treatment of FB1 did not alter the amount of liver [3H]-AFB1 DNA adducts, which suggested that FB1 promotion of AFB1 did not involve Phase I or Phase II metabolism of AFB1. The FB1 promotional activity was closely correlated with evidence of disruption of sphingolipid metabolism suggesting that alterations in associated signaling pathways, known to control cell growth and apoptosis, are potentially responsible for the promotional activity of FB1.