Carcinogen

The international pictogram for chemicals that are mutagens, carcinogens or teratogens.

A carcinogen or carcinogen is a physical, chemical or biological agent potentially capable of causing cancer when exposed to living tissue. Based on the above, a carcinogen is a physical or chemical agent that can produce a neoplasm.

Chemical carcinogens are defined by the ability to develop tumor types not seen in controls; by a higher incidence of some tumor in the exposed animals than in the unexposed ones, or by the earlier appearance of tumors in comparison with the controls. DDT (dichlorodiphenyltrichloroethane), benzene and asbestos have been classified as carcinogens. Tobacco has also been identified as a risk source for several types of cancer. Carcinogens are also frequently, but not necessarily, teratogenic or mutagenic.

Biomedical importance

It is accepted that 90% of human cancers are caused by environmental or nutritional factors that induce a process of carcinogenesis. These include smoking, certain dietary habits, and chemicals and drugs. It is estimated that the remaining 10% is due to genetic, viral and radiation factors.

Identification

Identifying carcinogens is difficult. Most of the carcinogenic effects of chemicals have a long latency period; it is not uncommon for 20 to 30 years to elapse before tumors develop. These delayed effects are rarely detected in the first clinical trials of new drugs. Chemicals capable of causing cancer in laboratory animals have diverse structures, suggesting that many mechanisms are likely involved in inducing cancer. Carcinogenesis is believed to depend on different chemical promoters and to be a multiphasic process, from the initiation of cellular changes to the development and proliferation of tumor cells. Most carcinogens are nonreactive compounds (procarcinogens or secondary carcinogens) that become primary carcinogens in the body.

Carcinogens in pharmacology

Detection of the carcinogenic potential of a drug with a low tumor incidence is a serious problem during the evaluation phase of new drugs. For example, it is normal for any study, whatever the dose, to use 100 animals (to reach statistical significance, the incidence of tumor development would have to be 4%, which is extremely high for most drugs).. Short-term mutagenicity studies are proving to be an effective and reasonable method of detecting potential carcinogens before large-scale studies are carried out in humans and may even become better predictors of carcinogenicity in humans.

Drugs with a high carcinogenic potential should be avoided, but therapeutic decisions depend on the benefit-risk ratio. For example, although alkylating chemotherapeutics are potent carcinogens in various animal species, it would be illogical to reject them in a patient with a life-threatening disease. It is a situation analogous to exposure to X-radiation, which also has a high carcinogenic potential.

Few drugs are used for which there is solid evidence that they are carcinogenic in humans. Rarely, oral contraceptives cause hepatic adenomas, tumors that are benign from the point of view of their growth, but are extremely vascular and can cause fatal bleeding. Some authors have made reference to the association between reserpine and breast carcinoma based on case control studies, but this finding could not be confirmed by means of cohort studies. There is convincing evidence that some non-drug chemicals are carcinogens. This evidence includes associations such as aflatoxins and hepatoma, vinyl chloride and hepatic hemangiosarcoma, coal tar and skin cancer, cigarette smoke and lung carcinoma, and aniline dyes and bladder tumors.