Indole-3-carbinol induces a rat liver glutathione transferase subunit (Yc2) with high activity toward aflatoxin B1 exo-epoxide. Association with reduced levels of hepatic aflatoxin-DNA adducts in vivo.
Aflatoxin B1 (AFB1), a metabolite of the grain mold Aspergillus flavus, is a potent hepatocarcinogen and widespread contaminant of human food supplies. AFB1-induced tumors or preneoplastic lesions in experimental animals can be inhibited by cotreatment with several compounds, including indole-3-carbinol (I3C), a component of cruciferous vegetables, and the well-known Ah receptor agonist beta-naphthoflavone (BNF). This study examines the influence of these two agents on the AFB1-glutathione detoxication pathway and AFB1-DNA adduction in rat liver. After 7 days of feeding approximately equally inhibitory doses of I3C (0.2%) or BNF (0.04%) alone or in combination, male Fischer 344 rats were administered [3H]AFB1 (0.5 mg/kg, 480 microCi/kg) intraperitoneally and killed 2 hr later. All three experimental diets inhibited in vivo AFB1-DNA adduction (BNF, 46%; I3C, 68%; combined, 51%). Based on Western blots using antibodies specific for the glutathione S-transferase (GST), subunit Yc2 (subunit 10) appeared to be substantially elevated by the diets containing I3C (I3C diet, 4.0-fold increase in band density; combined diet, 2.8-fold). The BNF diet appeared to elevate Yc2 to a lesser extent (2.2-fold increase in band density).(ABSTRACT TRUNCATED AT 250 WORDS)
Stresser
D M
DM
Department of Food Science and Technology, Oregon State University, Corvallis 97331-6602.
Williams
D E
DE
McLellan
L I
LI
Harris
T M
TM
Bailey
G S
GS
D016604:Aflatoxin B1 / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007536:Isomerism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D019324:beta-Naphthoflavone
D016588:Anticarcinogenic Agents; D001571:Benzoflavones; D018736:DNA Adducts; D007211:Indoles; D046911:Macromolecular Substances; C072611:aflatoxin B1-DNA adduct; C006426:aflatoxin B1-2,3-oxide; D019324:beta-Naphthoflavone; D004247:DNA; D016604:Aflatoxin B1; C016517:indole-3-carbinol; D005982:Glutathione Transferase