procarcinogen

A procarcinogen is a chemical that is not itself carcinogenic, or only weakly carcinogenic, but can become carcinogenic after metabolic activation within the body. Activation usually occurs through phase I enzymes, especially the cytochrome P450 family, which introduce reactive groups into the compound.

The metabolic activation often yields reactive intermediates, such as electrophilic epoxides or other short-lived species, that can interact with DNA to form adducts. These DNA lesions can cause mutations if not correctly repaired, contributing to the initiation of carcinogenesis. Activation can take place in the liver or in specific target tissues, influencing where cancer risk is greatest.

Detoxification pathways, including phase II conjugation reactions carried out by enzymes like glutathione S-transferases, UDP-glucuronosyltransferases, and sulfotransferases, can neutralize reactive intermediates and facilitate excretion. Individual susceptibility varies with genetics, age, diet, and exposure to substances that induce or inhibit activating enzymes, which can alter the balance between activation and detoxification.

Examples of procarcinogens include aflatoxin B1, benzo[a]pyrene, certain arylamines, and some N-nitrosamines. Aflatoxin B1 is converted to a DNA-reactive epoxide that forms adducts, while benzo[a]pyrene is oxidized to a diol epoxide capable of DNA alkylation.

Understanding procarcinogens is important for risk assessment and prevention, as the carcinogenic potential depends on metabolic context, exposure levels, and individual metabolic capability.