The Effect of Liver Regeneration on Tumor Formation in Rats Fed 4-Dimethylaminoazobenzene

Abstract

Many physical and chemical factors, without being carcinogenic themselves, are able to cause an augmentation of tumor production when properly combined with the action of a specific carcinogen. Physical factors shown to be capable of such an action are: mechanical irritation (1) and scalding (2). Chemical factors are: a basic fraction of creosote oil (3), turpentine and chloroform (4), croton oil and its active component, croton resin (5).The most important fact, with respect to the mechanism of action of these irritants, is that none of them is effective when applied before rather than after the specific carcinogen (6). They act only when the carcinogenic process has been started by a specific carcinogen and carried on up to a certain point. This point may be such that the histological picture of the tissue under consideration cannot be distinguished from the normal one (4).Valuable information concerning the effect of irritants may be gained by consideration of a series of investigations which deal with the tumor-promoting action of surgically induced cell regeneration. Wounds were produced by excision or cauterization of skin in areas previously treated with suboptimal doses of a carcinogen. The subsequent healing process was found greatly to augment tumor formation (4, 7). It seems probable, therefore, that the action of irritants is in some way similar to the action of traumatic factors in the sense that both induce cell regeneration.These findings were considered to indicate the existence of a stage characterized by the formation of ceils capable of forming tumors but not asserting

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

“…Partial hepatectomy during the course of feeding acetylaminofluorene (Laws, 1959) or dimethylaminoazobenzene (Glinos et al, 1951;Glinos, 1964) was thought to accelerate the development of tumours but not to influence the number produced; the duration of feeding and the consequent hyperplastic effects complicate the interpretation. CCl4-induced regeneration of the liver 30 days after a single carcinogenic dose of X-rays increased the yield of tumours (Cole and Nowell, 1965) and a similar result was reported after X-irradiation or neutron bombardment when CC14 was given up to 9 months later (Curtis et al, 1968).…”

Induction of Liver Cell Adenomata in the Rat by a Single Treatment with N-Methyl-N-Nitrosourea given at Various Times after Partial Hepatectomy

“…Following partial hepatectomy, a previously inactive compound may induce hepatomata (Warwick, 1967) or a liver carcinogen normally ineffective in a single dose may become effective (Marquardt et al, 1970;Craddock, 1971Craddock, , 1973a. Hepatectomy during the course of feeding of a carcinogen may reduce the latent period of tumour induction (Laws, 1959;Glinos, Bucher and Aub, 1951;Glinos, 1964) or may increase the size of the tumours (Hoffmann, 1970). The present results are consistent with these observations.…”

Modulation of Tumor Promotion in Liver Carcinogenesis

“…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.…”