Inhibition by dietary hydroquinone of acetylaminofluorene induction of initiation of rat liver carcinogenesis.
Monocyclic phenolics (MPs) occur widely in foods, both naturally and as synthetic antioxidant additives. Several have been shown to inhibit the carcinogenicity of a variety of genotoxic carcinogens in various tissues. Hydroquinone (HQ), one of the simplest of the MPs, which occurs naturally as the glucose conjugate arbutin, was studied for its ability, at low dietary levels, to inhibit the initiating effects in the rat liver of the DNA-reactive carcinogen 2-acetylaminofluorene (AAF). Male Fischer 344 rats (F344), 8 weeks old at the start of the study, were allocated to six groups. HQ was fed daily ad libitum in PMI certified diet at either 0.05% (approximately 25 mg/kg bw/d) or 0.2% (approximately 100 mg/kg bw/d) for 13 weeks, starting one week before AAF administration was initiated, and at the same doses to two groups not receiving AAF. AAF was given intragastrically three times a week for 12 weeks at doses of 3mg/kg bw in 0.5% carboxymethyl cellulose (CMC) to a basal diet group and two of the groups receiving HQ in the diet. Vehicle controls were fed basal diet and administered 0.5% CMC intragastrically three times a week. The rats were observed daily and body weights were taken before initial dosing and at weekly intervals thereafter. Body weight gain over time, terminal body weights and absolute (mg) and relative liver weights (relative to body weight) were measured. At the end of the study (13 weeks), DNA adducts ((32)P-postlabeling), cell proliferation (PCNA immunohistochemistry) and preneoplastic hepatocellular altered foci (HAF) (glutathione S-transferase-placental type immuno-histochemistry) were measured. No significant differences were observed in body weight gains or liver weights. AAF produced liver DNA adducts and at the low dose of HQ adduct levels were 90% of that for AAF alone, whereas at the high dose adducts were reduced by 33% (p<0.05). AAF exposure yielded about a 50% increase in hepatocellular proliferation and both HQ doses reduced the AAF-induced increases in proliferation by about 25%. Likewise, the AAF-induced GST-P-positive HAF per cm(2) of liver tissue were decreased by both doses of HQ by about 50%. Thus, under the conditions of this experiment, HQ at both 0.05% and 0.2% in the diet diminished AAF-induced cancer initiating effects in rat liver.
Williams
Gary M
GM
Department of Pathology, Basic Science Building, New York Medical College, Valhalla, NY 10595, USA. Gary_Williams@NYMC.edu
Iatropoulos
Michael J
MJ
Jeffrey
Alan M
AM
Duan
Jian-Dong
JD
D015073:2-Acetylaminofluorene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005503:Food Additives / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology*; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D009929:Organ Size; D011230:Precancerous Conditions; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D015430:Weight Gain / Q000187:drug effects
D000975:Antioxidants; D002273:Carcinogens; D018736:DNA Adducts; D005503:Food Additives; D006873:Hydroquinones; D015073:2-Acetylaminofluorene; C031927:hydroquinone