Prevention by 1'-acetoxychavicol acetate of the induction but not growth of putative preneoplastic, glutathione S-transferase placental form-positive, focal lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet.
The effects of 1'-acetoxychavicol acetate (ACA) on endogenous rat liver carcinogenesis because of chronic feeding of a choline-deficient, L-amino acid-defined (CDAA) diet were examined. Male Fischer 344 rats, 6 weeks old, received the CDAA diet containing ACA at doses of 0, 0.005, 0.010 and 0.050% for 12 weeks and were then killed. ACA decreased the numbers of putative preneoplastic, glutathione S-transferase placental form (GST-P)-positive, focal lesions developing in the livers of rats fed the CDAA diet but did not alter their sizes. At the same time, ACA reduced the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, but did not significantly affect generation of 2-thiobarbituric acid-reacting substances, indicators of oxidative extra-DNA damage, or hepatocyte proliferation. Furthermore, ACA did not exert any significant effects on the numbers or sizes of GST-P-positive lesions in the livers of rats when administered between weeks 2 and 8 after initiation with a single i.p. dose of 200 mg/kg body wt of N-nitrosodiethylamine. These results indicate that ACA prevents the CDAA diet-associated induction of putative preneoplastic lesions by reduction of oxidative DNA damage but does not affect their subsequent growth.
Kobayashi
Y
Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Nakae
D
D
Akai
H
H
Kishida
H
H
Okajima
E
E
Kitayama
W
W
Denda
A
A
Tsujiuchi
T
T
Murakami
A
A
Koshimizu
K
K
Ohigashi
H
H
Konishi
Y
Y
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001592:Benzyl Alcohols; D002273:Carcinogens / Q000494:pharmacology; D002794:Choline / Q000008:administration & dosage*; D004032:Diet; D004052:Diethylnitrosamine / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010920:Placenta / Q000201:enzymology; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000494:pharmacology*
D000596:Amino Acids; D016588:Anticarcinogenic Agents; D001592:Benzyl Alcohols; D002273:Carcinogens; D013729:Terpenes; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D002794:Choline; C047948:1'-acetoxychavicol acetate