DNA alkylating medications

DNA alkylating medications are a class of drugs that are mainly used as anticancer agents. They disrupt the structure of DNA by adding an alkyl group to the guanine base and can affect all phases of the cell cycle.

Alright, the cell cycle refers to the events that somatic cells, which includes all of the cells in our bodies except the reproductive cells, go through from the moment they’re formed until the moment they divide into two identical daughter cells. This cycle varies in length depending on the type of cell. For rapidly dividing cells, like skin cells, it takes less than a day, whereas for other cells, like liver cells, the cell cycle can last years.

Now, the cell cycle can be divided in two phases: interphase and mitosis. Interphase comprises of the G1 phase, during which the cell grows and performs its cell functions, the S phase, during which DNA is replicated, and the G2 phase, during which the cell grows again before entering mitosis. Mitosis can be broken down into prophase, metaphase, anaphase, and telophase, during which the replicated DNA divides equally for the two daughter cells, and ends with cytokinesis, which is when the cell membrane actually divides to form the two new cells. There’s also a G0 phase which is an extended G1 phase where the cell is resting and not actively preparing to divide.

Alright, now imagine a cancer cell. This cell is going through the phases of the cell cycle without regulation, and its DNA also replicates more frequently and with less error-correcting than healthy cells. Therefore, it’s more sensitive to DNA damage.

Here’s a DNA base, guanine. Alkylating agents attach an alkyl group at the number 7 nitrogen atom of guanine. Based on their mechanism of action, alkylating agents are characterized as monofunctional, or bifunctional. When monofunctional alkylating agents attach an alkyl group to guanine, repair enzymes recognize there’s something wrong, so they attempt to replace the alkylated bases and cause fragmentation of the DNA, or DNA strand breakage. When this section of the DNA is repaired, abnormal base pairing could result, like having a thymine paired up with guanine instead of the usual cytosine. Eventually, the DNA damage, that is caused by the monofunctional alkylating agents, can potentially lead to carcinogenesis, or development of cancer cells, or it can result in cell death.