Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats

Pound, A. W.; McGuire, Lloyd

doi:10.1038/bjc.1978.88

Cited by 74 publications

(35 citation statements)

References 23 publications

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“…THlE number of tumours produced in the liver of animals given a dose of diethylnitrosamine (DEN) is increased if they are previously subjected to partial hepatectomy (Griinthal et al, 1970) or treated with a hepatonecrotic dose of CC14 (Pound, 1978). The variation of the tumour yield with the interval between the two treatments has led to the opinion that the liver is more susceptible to the carcinogenic action when the cells are proliferating rapidly in the regenerative phase, although a particular susceptible phase of the cell cycle has not been demonstrated.…”

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confidence: 99%

Influence of repeated liver regeneration on hepatic carcinogenesis by diethylnitrosamine in mice

Poound¹,

McGuire²

1978

Br J Cancer

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Summary.-In mice given a single dose of diethylnitrosamine, a hepatonecrotic dose of carbon tetrachloride, 5 weeks after dosing with DEN and repeated 6 times at 4-weekly intervals, augmented the tumour yield in the livers. A single hepatonecrotic dose of CC14 24 h before a single dose of DEN also increased the number of tumours produced. The effect of the repeated administration of CC14 after the dose of DEN occurred in addition to, and was therefore independent of, the enhancing effect of a single dose of CC14 before DEN.These results may be interpreted as implying (1) that the liver in the regenerative phase after a hepatonecrotic dose of CC14 is more susceptible to an initiating action of DEN, i.e. produces more potential foci of tumour growth than in the normal liver and (2) that the repeated doses of CC14 leading to repeated phases of regeneration, after the dose of DEN, provide a promoting stimulus.

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confidence: 99%

Influence of repeated liver regeneration on hepatic carcinogenesis by diethylnitrosamine in mice

Poound¹,

McGuire²

1978

Br J Cancer

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“…Even though the role played in tumor promotion by both quantity and quality of dietary fat appears to be complex, it was of interest to find in the present study that there is no correlation between efficacy of the promotion and degree of stimulation of liver cells proliferation with CD diets containing different amounts of fat. Enhanced liver cell proliferation induced by a partial hepatectomy or a necrogenic dose of carbon tetrachloride has been shown to accelerate the development of liver tumors in rats or mice initiated with a variety of carcinogens (19)(20)(21)(22). However, our findings suggest that the general properties of enhanced cell proliferation per se are not the sole factors in determining the efficacy of tumor promotion in the liver and that other factors must be involved.…”

Section: Discussionmentioning

confidence: 54%

Modulation of Tumor Promotion in Liver Carcinogenesis

Satoh¹,

Abanobi²,

Lombardi³

1983

Environmental Health Perspectives

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Earlier, we demonstrated that feeding to rats a diet devoid of choline, a lipotropic factor, markedly enhances hepatoma induction by several chemical carcinogens, and that the diet acts as a strong promoter of the evolution of initiated cells to foci of altered hepatocytes. The ability of several factors to modulate the action of the choline-devoid (CD) diet as a promoter was investigated by quantitating the foci of y-glutamyl transpeptidase-positive hepatocytes developed in rats exposed to a single injection of diethylnitrosamine. Addition to the diet of phenobarbital (PHB) resulted in a promoting action stronger than those of the CD diet or of PHB alone. Two other barbiturates, amobarbital (AMB) and pentobarbital (PTB) exerted an effect similar to that of PHB, while barbituric acid (BA) had no effect. In other studies, lowering the fat content of the CD diet reduced its efficacy as a promotor, while the addition of a hypolipidemic agent, BR931, 4-chloro-642,3 xylidino)-2-pyrimidinylthio (N-p-hydroxy-ethyl)acetamide, completely abolished the promoting action of the CD diet. In rats not exposed to carcinogen, feeding the CD diet caused a marked enhancement of liver DNA synthesis and of cell proliferation. Inclusion of PHB, PTB or AMB in the CD diet inhibited these effects, while BA exerted no inhibition. The increased rate of DNA synthesis and cell proliferation in the liver were not affected by the level of fat in the CD diet. These results suggest that beside a stimulation of liver cell proliferation, other factor(s) determine the efficacy with which a CD diet exerts its promoting action.

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“…A number of experimental findings suggest that proliferative stimuli such as those exerted by PH or necrogenic doses of CCl4 promote the appearance of nodules and hepatocellular carcinomas after initiation with different carcinogens (21)(22)(23). In contrast, conflicting information comes from studies where mitogens were used as promoting agents in long-term regimens.…”

Section: Development Of Foci and Nodulesmentioning

confidence: 99%

Compensatory Regeneration, Mitogen-Induced Liver Growth, and Multistage Chemical Carcinogenesis

Ledda-Columbano¹,

Coni²,

Simbula³

et al. 1993

Environmental Health Perspectives

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Liver cell proliferation has often been implicated to play a major role during different steps of the carcinogenic process. Most of the experimental studies indicating a close association between cell proliferation and liver cancer development have made use of a compensatory type of proliferative stimulus. However, liver growth may also be caused by direct hyperplasia after administration of primary mitogens. Our recent studies examined the possible differences between these two types of cell proliferation. Our studies indicate that a) increased expression of proto-oncogenes such as c-fos, c-jun, and c-myc is not necessary for entry into the cell cycle during mitogen-induced liver growth; b) mitogen-induced liver growth does not support initiation of chemical hepatocarcinogenesis; c) repeated proliferative stimuli induced by primary mitogens do not stimulate the growth of initiated cells to a focal and/or nodular stage; and d) mitogen-induced liver growth, unlike compensatory regeneration, is followed by a particular mode of cell death, namely, apoptosis. This type of cell death may be responsible for the elimination of carcinogen-initiated cells.

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Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats

Cited by 74 publications

References 23 publications

Influence of repeated liver regeneration on hepatic carcinogenesis by diethylnitrosamine in mice

Influence of repeated liver regeneration on hepatic carcinogenesis by diethylnitrosamine in mice

Modulation of Tumor Promotion in Liver Carcinogenesis

Compensatory Regeneration, Mitogen-Induced Liver Growth, and Multistage Chemical Carcinogenesis

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