Mutagenicity and Carcinogenicity

Drug-induced modification of DNA is called mutagenicity. If the mutations affect the tumor suppressor genes or proto-oncogenes, it can lead to carcinogenesis.

Carcinogenesis begins with tumor initiation. Here, a genotoxic carcinogen—called an initiator—mutates a gene to inhibit cellular apoptosis and promote proliferation.

This is followed by the tumor promotion step, where an epigenetic carcinogen —called a promoter—alters the cellular environment to promote the survival of pre-cancerous cells.

The IARC categorizes chemicals into four groups based on their carcinogenic potential.

The genotoxic potential of such carcinogens is assessed using in vitro and in vivo tests.

In vitro mutagenicity tests such as the Ames test, chromosome aberrations and sister chromatid exchange assays are rapid and inexpensive, but they can have some false results.

In vivo carcinogenicity tests involve chronic dosing in animals, followed by the detection of tumors. Although expensive and time-consuming, they are required to assess the risks to human health.