Antagonism, carcinogenic

Anticarcinogens that either directly antagonize carcinogens, or more likely prevent their activation, are also present in many foods naturally or are added to them. Included in this list of good guys are vitamins A, E, and C, some Bs, chlorophyll, carotene, butylated hydroxytoluene (BHT), and anisole (BHA). Many of these substances are effective antioxidants that presumably may inhibit oxidative carcinogenic activation. Vitamin C is also a potent inhibitor of nitrosamine formation. 

The antagonism or prevention of toxic effects may also benefit from stereochemical principles. Thus, optically active flavanones have been shown to inhibit the metabolic activation of the carcinogen benzo[a]pyrene to metabolites that bind covalently to DNA (Chae et al., 1992). Moreover, the (+) enantiomers of 3-0-methyicatechin and catechin have been demonstrated to protect stereoselectively against lipid peroxidation due to paracetamol (Devalia et al., 1982),... 

Severe adverse drug reactions with trimethoprim and co-trimoxazole are rare (12-14). This also applies to children (15). The adverse effects of co-trimoxazole correspond to those expected from a sulfonamide (16). In HIV-infected patients, adverse effects of co-trimox-azole are more frequent and more severe (17-19). Hematological disturbances due to co-trimoxazole include mild anemia, leukopenia, and thrombocytopenia, which may be due to folic acid antagonism. Serious metabolic disturbances that are associated with trimethoprim include hyperkalemia and metabolic acidosis. Trimethoprim can cause hypersensitivity reactions. However, with co-trimoxazole, the sulfonamide is generally believed to be more allergenic (12). Generalized skin reactions predominate. Other effects, such as anaphylactic shock, are extremely rare (20-22). Carcinogenicity due to trimethoprim or co-trimoxazole has not been reported. 

In order to explain an antagonism phenomenon which they had observed Lacassagne, Buu-Hoi, Daudel, and Rudali42 imagined that carcinogenic hydrocarbons must be capable of forming an addition complex with the substrate which determines cellular division and that this addition is only effective for the production of carcinomas if it takes place at certain definite points in the cell. 

Methylacrylonitrile is a mild skin and eye irritant. However, it is readily absorbed by skin. It showed delayed skin reaction. In mice, the lethal dose from intraperitoneal administration was 15 mg/kg. The oral toxicity due to this compound was also relatively high an LD50 of 11.6 mg/kg was determined in mice. There is no report of its mutagenic, teratogenic, or carcinogenic actions in animals or humans. 4-Dimethylaminophenol [616-60-3] plus sodium thiosulfate or N-acety Icy stein [616-91-1] was shown to antagonize the acute toxicity of methylacrylonitrile (Peter and Bolt 1985). 

Figure 4. Schematic of a mechanism, based on enzyme induction, by which chemical carcinogen B antagonizes the carcinogenic action of chemical carcinogen A as observed in the effect described by Richardson and Cunningham (see Figure 2) (52).

Chronic experiments using combined exposures to multiple carcinogenic metals, such as would occur most frequently in human exposures (Waalkes and Oberdorster 1990), have not been carried out with cadmium. However, cadmium can both enhance and antagonize the carcinogenic effects of several organic carcinogens (Harrison and Heath 1986 Kurokawa et al. 1985 Wade et al. 1987 Waalkes et al. 1991c). The incidence of diethyl-... 

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