title: Inhibition by N-(4-hydroxyphenyl)retinamide and all-trans-retinoic acid of exogenous and endogenous development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in the livers of rats.
abstract: The effects of N-(4-hydroxyphenyl)retinamide (4-HPR) and all-trans-retinoic acid (tRA) on the exogenous and endogenous models of rat liver carcinogenesis respectively using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous study, male Fischer 344 rats, 6 weeks old, were given a single i.p. dose of 200 mg/kg body wt of DEN, partially hepatectomized at week 3, administered 4-HPR at doses of 0, 0.04, 0.08 and 0.16% or tRA at 0, 0.004, 0.008 and 0.015% in diet from week 2 for 6 weeks, and killed at the end of week 8. For the endogenous study, rats were fed the CDAA diet containing 4-HPR or tRA for 12 weeks and killed at the end of week 12. 4-HPR decreased the numbers and sizes of the glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, the levels of 8-hydroxyguanine (8-OHG), a parameter of oxidative DNA damage, and the bromodeoxyuridine labeling indices (BrdU L.I.) by all three doses in the DEN-initiated case and, more prominently, in the CDAA diet-associated case. In contrast, while tRA failed to exert inhibitory effects apparently on foci development, 8-OHG formation or BrdU labeling in the DEN-initiated case, it reduced the numbers and sizes of the foci, the 8-OHG levels and the BrdU L.I. by all three doses in the CDAA diet-associated case. Furthermore, both 4-HPR and tRA inhibited the CDAA diet-associated induction of hepatocyte necrosis and connective tissue increase but not intrahepatocellular fat accumulation. These results indicate that 4-HPR exerts chemopreventive effects against the exogenous and endogenous rat liver carcinogenesis, while tRA can inhibit only the latter.
authors.affiliation: Department of Oncological Pathology, Cancer Center, Nara Medical University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: D
authors.initials: D
authors.lastname: Nakae
authors.forename: K
authors.initials: K
authors.lastname: Horiguchi
authors.forename: H
authors.initials: H
authors.lastname: Akai
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Andoh
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: A
authors.initials: A
authors.lastname: Denda
authors.forename: T
authors.initials: T
authors.lastname: Tsujiuchi
authors.forename: H
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002796:Choline Deficiency / Q000150:complications; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D017313:Fenretinide / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008297:Male; D010920:Placenta / Q000201:enzymology*; D011230:Precancerous Conditions / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D017313:Fenretinide; D014212:Tretinoin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D001973:Bromodeoxyuridine; D003849:Deoxyguanosine