Metabolic Activation of Epigenetic Carcinogens

Since there is no common mechanism describing the action of epigenetic carcinogens, generalizations concerning the effect of metabolism on the activity of chemicals acting by a nongenotoxic mechanism are not possible. The activity of a number of epige-netic carcinogens is reduced as a result of metabolic activation, although in the case of one group of epigenetic carcinogens that produce renal tumors in the rat by binding to and preventing the degradation of a specific kidney protein, alpha-2-microglobulin, metabolic activation is required for carcinogenic activity. Compounds acting by this mechanism include isophorone and D-limonene, which are present naturally in many fruits.

Similarly, a wide range of structurally diverse chemicals induce liver tumors in rodents due to their ability to induce the proliferation of hepatic peroxisomes. Food contaminants such as phthalate diesters, which leach out of packaging materials, fall into this category, although no naturally occurring food chemical has yet been found to be a peroxisome proliferator. Some examples of nonge-notoxic mechanisms of carcinogenesis are shown in Table 3.

Table 3 Some examples of nongenotoxic mechanisms of carcinogenesis

Mechanism

Examples of chemical classes

Promotion

Phorbol esters; barbiturates; chlorinated

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