Positive influence of dietary deoxycholic acid on development of pre-neoplastic lesions initiated by N-methyl-N-nitrosourea in rat liver.
The effect of deoxycholic acid (DCA) treatment subsequent to initiation of F344 male rats with N-methyl-N-nitrosourea (MNU), a wide spectrum carcinogen inducing tumors in many organs, was investigated. Rats were initially given four doses of MNU (50 mg/kg) i.p. within a 2-week period combined with a two-thirds partial hepatectomy performed at day 7 and then placed on basal diet containing DCA at concentrations of 0.313, 0.125, 0.050 and 0.020% for 21 weeks prior to final sacrifice. All organs studied were carefully examined histologically and histochemically for development of neoplastic and pre-neoplastic lesions. DCA enhanced the induction of glutathione S-transferase positive (GST-P+) liver cell foci in a dose-related manner. Furthermore groups of rats given DCA without prior MNU administration also developed dose-dependent numbers of pre-neoplastic liver lesions. In addition, increased numbers of small intestine tumors were apparent in DCA-treated animals although the difference was not significant. Induction of tumors in the thyroids, Zymbal glands, skin and peripheral nerves was not affected. The results indicate that DCA is a strong promoter of hepatocarcinogenesis with possible complete carcinogenicity in the liver and promotion potential for tumor development in the small intestine.
Tsuda
H
H
First Department of Pathology, Nagoya City University Medical School, Japan.
Asamoto
M
M
Kagawa
M
M
Uwagawa
S
S
Inoue
K
K
Inui
M
M
Ito
N
N
D000818:Animals; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D008770:Methylnitrosourea; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D003840:Deoxycholic Acid; D008770:Methylnitrosourea