Fumonisin B1 promotes aflatoxin B1 and N-methyl-N'-nitro-nitrosoguanidine-initiated liver tumors in rainbow trout.
Laboratory studies have described the carcinogenicity of fumonisin B1 (FB1) in rodents and epidemiological evidence suggests an association between FB1 (a mycotoxin produced by Fusarium moniliforme) and 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 promoter of liver tumors in fish initiated as fry with aflatoxin B1 (AFB1); and (iii) a promoter of liver, kidney, stomach, or swim bladder tumors in fish initiated as fry with N-methyl-N'-nitro-nitrosoguanidine (MNNG). FB1 was not a complete carcinogen in trout. No tumors were observed in any tissue of fish fed diets containing 0, 3.2, 23, or 104 ppm FB1 for a total of 34 weeks (4 weeks FB1 exposure, 2 weeks outgrowth on control diet, followed by 30 weeks FB1 diet) in the absence of a known initiator. FB1 promoted AFB1 initiated liver tumors in fish fed > or = 23 ppm FB1 for 42 weeks. A 1-week pretreatment of FB1 did not alter the amount of liver [3H]AFB1 DNA adducts, which suggests that short-term exposure to FB1 will not alter phase I or phase II metabolism of AFB1. In MNNG-initiated fish, liver tumors were promoted in the 104 ppm FB1 treatment (42 weeks), but FB1 did not promote tumors in any other tissue. Tumor incidence decreased in kidney and stomach in the 104 ppm FB1 treatment of MNNG-initiated trout. The FB1 promotional activity in AFB1-initiated fish was correlated with disruption of sphingolipid metabolism, suggesting that alterations in associated sphingolipid signaling pathways are potentially responsible for the promotional activity of FB1 in AFB1-initiated fish.
Center for Molecular Toxicology, Penn State University, 226 Fenske Lab, University Park, Pennsylvania 16802, USA.
D B
DB
Carlson
D E
DE
Williams
J M
JM
Spitsbergen
P F
PF
Ross
C W
CW
Bacon
F I
FI
Meredith
R T
RT
Riley
D016604:Aflatoxin B1 / Q000633:toxicity*; D000400:Air Sacs / Q000187:drug effects / Q000473:pathology; D000818:Animals; D002264:Carboxylic Acids / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D004357:Drug Synergism; D037341:Fumonisins; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009183:Mycotoxins / Q000633:toxicity*; D017686:Oncorhynchus mykiss; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology
D002264:Carboxylic Acids; D002273:Carcinogens; D037341:Fumonisins; D009183:Mycotoxins; D008769:Methylnitronitrosoguanidine; C056933:fumonisin B1; D016604:Aflatoxin B1; D013110:Sphingosine; C005682:safingol