Chronic Alcoholism Enhances Hepatocarcinogenicity of Diethylnitrosamine in Rats Fed A Marginally Methyl–Deficient Diet

Porta, Eduardo A.; Markell, Nalani; Dorado, Russell D.

doi:10.1002/hep.1840050610

Cited by 41 publications

(13 citation statements)

References 21 publications

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“…HBV-DNA and HCV-RNA were not detected in the liver tissue of patients with alcoholic liver cirrhosis with HCC who had neither HBsAg nor HCV Ab [Horiike et al, 19891, suggesting that alcohol itself might have an oncogenic effect as shown in experimental models [Porta et al, 1985;Takada et al, 19851. On the other hand.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus plus‐ and minus‐ strand RNA in hepatocellular carcinoma and adjoining nontumorous liver

Horiike

Nonaka

Kumamoto

et al. 1993

Journal of Medical Virology

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The presence of hepatitis C virus (HCV) RNA in serum and liver tissue was examined in seven patients with hepatocellular carcinoma (HCC), using the reverse transcriptase-polymerase chain reaction method with primers for the 5'-noncoding region. Plus-strand HCV-RNA was detected in the serum and liver tissue (both cancerous and noncancerous tissue) of all five patients who were positive for anti-HCV antibodies (C100-3 and P22) and was not detected in both of two patients who were negative for anti-HCV antibodies. Minus-strand HCV-RNA was only detected in the liver tissue (cancerous and noncancerous portion) of the five anti-HCV antibody-positive patients. The relative liver tissue content of minus-strand HCV-RNA ranged from 1 to 100 time less than that of plus strand HCV-RNA in cancerous and noncancerous tissue in each patient, respectively. There was no similar tendency in the HCV-RNA content between the cancerous and noncancerous portions of the liver in each patient. These results suggest that HCV exists and replicates in HCC tissue and may have some role in the development of HCC.

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Section: Discussionmentioning

confidence: 99%

Hepatitis C virus plus‐ and minus‐ strand RNA in hepatocellular carcinoma and adjoining nontumorous liver

Horiike

Nonaka

Kumamoto

et al. 1993

Journal of Medical Virology

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“…By both weeks, no significant differences were found in the apoptotic index among the 3 groups. (Porta et al, 1985;Takada et al, 1986) to no effect (Schmahl et al, 1965) to a protective effect (Habs and Schmahl, 1981). Our present study showed that prolonged i.p.…”

Section: Odc Activity Labeling Index and Apoptotic Index In The Livermentioning

confidence: 99%

Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N‐nitrosomorpholine

Tatsuta¹,

Baba²,

Yano³

et al. 1997

Int. J. Cancer

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The effects of ethyl alcohol (EtOH) during or after treatment with N-nitrosomorpholine (NNM) on hepatocarcinogenesis, ornithine decarboxylase (ODC) activity and the labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of 1 g EtOH/kg body weight every other day during or after treatment with NNM. Preneoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P), were examined immunohistochemically. At the end of experiment at week 16, administration of EtOH after NNM treatment had no significant effect on the number and size of GST-P-positive hepatic lesions, whereas administration of EtOH during NNM treatment significantly increased the number and percentage area but not the mean area of GST-P-positive hepatic lesions. EtOH caused significant increases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and the adjacent hepatocytes after the cessation of EtOH administration but not during EtOH treatment. Our findings indicate that EtOH enhances hepatocarcinogenesis and suggest that this effect may be closely related to the increases in ODC activity and cell proliferation in enzyme-altered lesions and the adjacent liver after EtOH treatment. Int. J. Cancer 71:1045-1048, 1997.r 1997 Wiley-Liss, Inc.Consumption of alcoholic beverages has been linked to an increased risk of hepatocellular carcinoma (HCC) in humans. Case-control studies (Oshima et al., 1984;Tsukuma et al., 1990) of HCC and alcohol consumption have shown a significantly increased risk of HCC in heavy drinkers. Ethanol (EtOH) also has been found to enhance hepatic tumorigenesis (Yamagiwa et al., 1994). However, the mechanism by which alcohol induces cancers in humans is not clear.Epidemiologically, Tsukuma et al. (1993) have reported that the risk of HCC is significantly increased in former heavy drinkers but is small and insignificant in current heavy drinkers. These findings suggest that alcohol at an initiation phase may have an important role in hepatocarcinogenesis. Therefore, to investigate this possibility, in the present work, we examined the effect of EtOH given during or after administration of the carcinogen N-nitrosomorpholine (NNM) on hepatocarcinogenesis in rats. MATERIAL AND METHODS AnimalsNinety inbred Sprague-Dawley rats, initially weighing 150 g, were purchased from Japan SLC (Shizuoka, Japan). Rats were housed in suspended cages with wire mesh bottoms in a room with controlled temperature (21 6 1°C) and humidity (40 6 10%) and a 12:12 light:darkness cycle and given free access to regular chow pellets (Nihon-Nosan, Yokohama, Japan). Experimental designAnimals were randomly divided into 3 groups of 30 rats each and from the beginning of the experiment were given drinking water containing 175 mg/l of NNM (Sigma, St. Louis, MO) for 8 weeks. NNM was dissolved in distilled water at a concentration of 50 g/l and stored in a cool place. The stock solution ...

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“…The hepatic TG content in methyl-deficient rats was higher than that of methylsupplemented rats, with ethanol reinforcing the difference. Thus, the effect of alcohol may not be direct but mediated through increasing methyl deficiency (Porta et al, 1985). Misslbeck et al (1984) limited their experiments to 12 weeks, and did not observe development of liver tumors.…”

Section: Discussionmentioning

confidence: 98%

“…Takada et al (1986) did not report the percentage incidence of rats with liver nodules, and they could not confirm the presence of HCCs. Porta et al (1985) report that ethanol enhances the induction of liver tumors by DEN only when the rats are fed a marginally methyl-deficient diet. The hepatic TG content in methyl-deficient rats was higher than that of methylsupplemented rats, with ethanol reinforcing the difference.…”

Section: Discussionmentioning

confidence: 99%

Effect of ethanol on hepatocarcinogenesis initiated in rats with 3′‐methyl‐4‐dimethylaminoazobenzene in the absence of liver injuries

Yanagi

Yamashita

Hiasa

et al. 1989

Intl Journal of Cancer

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In this study special care was taken to discriminate between the direct effect of ethanol on hepatocarcinogenesis and secondary effects such as choline deficiency or fatty liver. Rats were divided into 2 groups, D and N. Group D was initiated using 3'-Me-DAB, while the control group N was not initiated. Groups N and D were divided into 4 sub-groups. Each subgroup was given, in the drinking water, one of the following ethanol solutions: 0, 5, 10 or 15% for 45 weeks. Liver tumors were induced only in D groups. Evidence obtained indicates that: (a) in the N group, ethanol did not cause any apparent disorders in histology and lipid metabolism, and (b) in the D group no significant differences were observed in the incidence of HCCs and other liver lesions. Ethanol thus does not appear to enhance hepatocarcinogenesis, at least in the absence of liver injury.

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Chronic Alcoholism Enhances Hepatocarcinogenicity of Diethylnitrosamine in Rats Fed A Marginally Methyl–Deficient Diet

Cited by 41 publications

References 21 publications

Hepatitis C virus plus‐ and minus‐ strand RNA in hepatocellular carcinoma and adjoining nontumorous liver

Hepatitis C virus plus‐ and minus‐ strand RNA in hepatocellular carcinoma and adjoining nontumorous liver

Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N‐nitrosomorpholine

Effect of ethanol on hepatocarcinogenesis initiated in rats with 3′‐methyl‐4‐dimethylaminoazobenzene in the absence of liver injuries

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