How do alkylating agents cause cancer?

Alkylating agents were among the first anti-cancer drugs and are the most commonly used agents in chemotherapy today. Alkylating agents act directly on DNA, causing cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing.

Which anticancer drug is an alkylating agent?

Eventually, the cancer cell dies. Alkylating agents were one of the first classes of drugs to be used against cancer. There are five traditional categories of alkylating agents: Nitrogen mustards (eg, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan)

How do alkylating agents target cancer cells?

Alkylating agents work by destroying the DNA in cancer cells. This is done by replacing alkyl groups with hydrogen atoms in the DNA so the cells can’t repair themselves. As a result, the lack of functioning DNA prevents cancer cell division and replication.

Can alkylating agents be carcinogenic?

Alkylating agents are classic carcinogens (methylnitrosourea, 7,12-dimethylbenzanthracene, diethylnitrosoamine) and also they are classic anticancer drugs (melphalan, chlorambucil, busulfan, cyclophosphamide, the nitrosoureas, cisplatinum and carboplatin).

What causes alkylation damage?

Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g. methylnitrosourea, tobacco-specific nitrosamines and drugs like temozolomide or streptozotocin, form adducts at N- and O-atoms in DNA bases.

How do alkylating agents induce mutations?

Mutagenicity is related to the ability of alkylating agents to form crosslinks and/or transfer an alkyl group to form monoadducts in DNA. The most frequent location of adducts in the DNA is at guanines. Expressed mutations involve different base substitutions, including all types of transitions and transversions.

Why are alkylating agents toxic?

Most alkylating agents cause gastrointestinal side effects and dose-limiting toxicity to bone marrow. Most of the alkylating agents produce an acute suppression of the bone marrow, with the major effect being a decreased granulocyte count. Busulfan depresses all blood elements, particularly stem cells.