Inhibitory effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), green tea catechins and other antioxidants on 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1)-induced rat hepatocarcinogenesis and dose-dependent inhibition by HTHQ of lesion induction by Glu-P-1 or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx).
The effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), green tea catechins (GTC), alpha-tocopherol, beta-carotene, chlorophyllin, phenylethylisothiocyanate (PEITC), 3-O-ethylascorbic acid (EAsA), 3-O-dodecylcarbomethyl ascorbic acid (DAsA), n-tritriacontane-16,18-dione (TTAD) and d-limonene on 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1)- or dimethylnitrosamine (DMN)-induced hepatocarcinogenesis, and the dose dependence of HTHQ inhibition of Glu-P-1- or 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx)-influence on lesion development were examined in a rat medium-term liver bioassay system featuring diethylnitrosamine initiation and partial hepatectomy. At the end of week 8, the number and total area of glutathione S-transferase placental form (GST-P) positive liver foci in rats treated with 0.03% Glu-P-1 alone were increased significantly (46.8 +/- 11.0 and 12.0 +/- 5.6 respectively) as compared to the control values (3.8 +/- 1.6 and 0.4 +/- 0.2). Combined treatment with 1% HTHQ remarkably reduced both of these parameters (8.1 +/- 2.1 and 0.6 +/- 0.2). GTC (1%), PEITC (0.1%), beta-carotene (0.1%) and DAsA (1%) also demonstrated inhibition but less than HTHQ. On the other hand, these antioxidants did not influence development of foci initiated by 0.002% DMN. In the dose-response study, up to 0.125% HTHQ significantly reduced the effects of 0.02% Glu-P-1 or 0.03% MeIQx on the number and area of foci. These results indicate that several antioxidants exert chemopreventive effects against heterocyclic amine (HCA)-induced hepatocarcinogenesis, and particularly HTHQ which thus deserves further attention as a chemopreventor in the contest of the environmentally important HCA group of carcinogens.
Hirose
M
M
First Department of Pathology, Nagoya City University, Medical School, Japan.
Hasegawa
R
R
Kimura
J
J
Akagi
K
K
Yoshida
Y
Y
Tanaka
H
H
Miki
T
T
Satoh
T
T
Wakabayashi
K
K
Ito
N
N
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002392:Catechin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006873:Hydroquinones / Q000494:pharmacology; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013662:Tea / Q000737:chemistry
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D006873:Hydroquinones; D007093:Imidazoles; D011804:Quinolines; D013662:Tea; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C081906:1-O-hexyl-2,3,5-trimethylhydroquinone; D002392:Catechin; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline