Liver carcinogenicity

A number of animal studies suggest that hepatomas occur only after liver necrosis and fibrosis have occurred and, therefore, that carbon tetrachloride is not a direct liver carcinogen." One early study, however, found that liver necrosis and its associated chronic regenerative state probably were not necessary for tumor induction, although a correlation was found between the degree of liver necrosis and the incidence of hepatomas. "... 

Toxicology. Heptachlor epoxide is a liver carcinogen in rodents. 

Lijinsky, W., Taylor, H.W. and Keefer, L.K., "Reduction of Rat Liver Carcinogenicity of 4-Nitrosomorpholine by a-Deuterium Substitution", J. Natl. Cancer Inst., 1976, 51, 1311-1313. 

A similar example is 2,6 dinitrotoluene where reduction in rats of a nitro group to a hydroxylamine occurs, which yields a liver carcinogen (see chap. 5). 

A particularly interesting example of the separation of modification is provided by estragole (88), which is a mouse two toxicities by structural liver carcinogen (81MI10506)... 

Liver toxin and animal liver carcinogen Monocrotaline. Toxic alkaloid present in certain Crotalaria plants... 

The product once was used to color edible fats and therefore was known as Butter Yellow, but its use to color food is prohibited because it is reported to be a potent liver carcinogen for rats. 

Williams GM, Iatropoulos M, Cheung R, Radi L, Wang CX. Diethylstilbestrol liver carcinogenicity and modification of DNA in rats. Cancer Lett 1993 68(2-3) 193-8. 

Some naturally occurring liver carcinogens are aflatoxin, cycasin, and safrole. A number of synthetic chemicals have been shown to cause liver cancer in animals, including the dialkylnitrosamines, dimethylbenzanthracene, aromatic amines such as... 

All of the seeming paradoxes above can be resolved by remembering the difference between prediction and postdiction. You should be astonished if someone tells you in advance that you will pick the three of spades, the six of diamonds, and the eight of diamonds. You should be concerned if a town with a factory which produces a known liver carcinogen shows a statistically significant incidence of increased liver cancer. And if anyone can tell you for sure that the lottery ticket you are about to purchase will be a winner, by all means do it. 

The most common source of aflatoxins is moldy food, particularly nuts, some cereal grains, and oil seeds. The most notorious of the aflatoxins is aflatoxin B1( for which the structural formula is shown in Figure 19.1. Produced by Aspergillus niger, it is a potent liver toxin and liver carcinogen in some species. It is metabolized in the liver to an epoxide (see Section 7.3). The product is electrophilic with a strong tendency to bond covalently to protein, DNA, and RNA. Other common aflatoxins produced by molds are those designated by the letters B2, G1( G2, and M,. 

Experiments with other congeners showed that chronic exposure to a mixture of 1,2,3,6,7,8-HxCDD and 1,2,3,7,8,9-HxCDD by gavage induced hepatocellular carcinoma, adenoma, and neoplastic nodules at approximately 0.34 g/kg/day in female Osbome-Mendel rats and at 0.71 g/kg/week in B6C3F, male mice (NCI/NTP 1980). Therefore, HxCDD is approximately 1/20 as potent a liver carcinogen as... 

There is little in the literature relative to vitamin A and colon cancer in human populations. Experimental animal studies, however, strongly suggest that vitamin A deficiency may have a role in this type of cancer. We have shown that a deficiency of vitamin A increased DMH-induced tumors and shortened the lag time for induction, compared to normally supplemented controls (72). More recently (73) we have confirmed a protective role for vitamin A in colon carcinogenesis (Table XVII). Furthermore, we have shown (74) that vitamin A deficiency can result in colon tumors in rats given aflatoxin (AFB ) which is normally a liver carcinogen (Table XVIII). The colon tumors associated with the hepatocarcinogen AFB.. appear to be a result of differences in metabolism and binding of AFB or its metabolite ) to colon DNA under conditions of vitamin A deficiency (75). 

Significant advances have been made in recent years in the understanding of the mechanisms of liver carcinogenicity of DEHP in rats and mice. However, there is increasing mechanistic evidence suggesting that rats and mice are not an appropriate model for extrapolating to humans (Cattley et al. 1998 Doull et al. 1999 Huber et al. 1996). Therefore, speculation on how to prevent liver cancer in humans based on information in rodents seems without scientific basis. 

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