Nucleophilic Substitution and Cancer

Agents that can cause cancer in either laboratory animals or humans are called carcinogens. Many different types of chemicals may act as carcinogens. Among these are certain alkylating agents, compounds which can act as substrates in nucleophilic substitutions. For example, chloromethyl methyl ether and bis(2-chloroetheyl)amine are both active carcinogens.

One theory of carcinogenesis, or how these compounds interact with cells, is that cellular nucleophiles displace the leaving group (chloride in these compounds) to form a bound adduct.

Cellular nucleophiles may include functional groups such as -NH2, -SH and -OH, all of which are abundant in the molecules that make up living systems, such as proteins and nucleic acids. The bound adduct changes the shape of the biomolecule by changing its molecular composition. A change in shape will often lead to a change in the function of the molecule, and this can, in turn, lead to a cancer-causing mutation of the cell.

An interesting point can be made about the carcinogenic amine (ClCH2CH2)2NH2, known as nitrogen mustard. This compound is also used to treat certain forms of cancer as a chemotherapy agent. The same mechanism by which a cell becomes cancerous -- disruption of the normal functioning of the cell through a mutation -- is used to kill cancer cells. Because cancer cells are rapidly dividing, they are more susceptible to mutation-causing chemicals such as nitrogen mustard than normal body cells.