Modulation of mycotoxin and nitrosamine carcinogenesis by indole-3-carbinol: quantitative analysis of inhibition versus promotion.
The value of chemopreventive agents for reducing human response to mycotoxins and N-nitrosamines remains uncertain, especially since many such agents also can act as tumour promoters. Indole-3-carbinol (I3C) from cruciferous vegetables can inhibit DNA adduction and hepatocarcinogenesis induced by aflatoxin B1 (AFB1) or N-nitroso-diethylamine in trout if given before and with the carcinogen but promotes carcinogenesis when given after initiation. Similar results have been obtained with I3C and AFB1 in rats. In detailed studies using 10,000 trout, inhibition of AFB1 carcinogenesis was found to be saturable at high doses of I3C, approximately proportional to dose of I3C through the range of human intake and, within this range, quantitatively predicted by I3C-mediated reduction of AFB1-DNA adduction in liver. In a second study, post-initiation promotion of AFB1 carcinogenesis was approximately proportional to I3C dose, increased with duration of exposure, decreased with delayed onset of exposure, and reduced but still significant when I3C was given on alternate months or weeks or twice per week only. Hence, promotion by this common component of cruciferous vegetables required prolonged exposure but not necessarily on a daily basis.
Bailey
G S
GS
Department of Food Science and Technology, Oregon State University, Corvallis.
Dashwood
R H
RH
Fong
A T
AT
Williams
D E
DE
Scanlan
R A
RA
Hendricks
J D
JD
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens; D004247:DNA / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control; D014337:Trout
D000348:Aflatoxins; D000975:Antioxidants; D002273:Carcinogens; D007211:Indoles; D004052:Diethylnitrosamine; D004247:DNA; D016604:Aflatoxin B1; C016517:indole-3-carbinol