Why carcinogens cause cancer?

DNA (Deoxyribonucleic acid), is a chemical found primarily in the nucleus of cells. DNA carries the instructions for making all the structures and materials the body needs to function.

DNA is organized as two complementary strands, head-to-toe, with bonds between them that can be "unzipped" like a zipper, separating the strands.

The sugar-phosphate backbones spiral around the outer surface of DNA.

Between these backbones are two different sized grooves, designated the major and minor grooves. The major groove is approximately 50% wider than the minor.

DNA Structure

Major grooves in a helix refer to the larger of the unequal grooves that are formed as a result of the double-helical structure of DNA.

Minor grooves in a helix refer to the smaller of the unequal grooves that are formed as a result of the double-helical structure of DNA.

Try this to see the two grooves!!

Click the right mouse button over the image
Render --> Schemes --> CPK

Proteins that interact with DNA often make contact with the edges of the base pairs that protrude into the major groove.

Carcinogens cause cancer by altering DNA in cells, interfering with normal biological processes. Usually cells are able to detect this and attempt to repair the DNA; if they cannot, they undergo cell death to prevent further damage. When the damage interferes with cell death or encourages cell division, cancer occurs. Rapidly dividing cells, such as in skin, the stomach lining, breast tissue, and reproductive organs, are particularly sensitive to carcinogens due to harmful DNA being quickly copied.

[ PDB: 1dxa]

Small carcinogen molecules generally bind to the minor grooves of DNA.

Try this to view clearly the carcinogen in the minor groove.

Click right mouse button over image
Select -->All
Style --> Scheme--> CPK
Select --> Hetero --> All
Color ---> Atoms --->Yellow --> Yellow

Tobacco smoke has also been identified as a rich source of dozens of carcinogens, including benzopyrene,

DNA damaged by Benzopyrene-diol-epoxide Benzopyrene is a chemical found in cigarette smoke. Benzopyrene is converted to Benzopyrene-diol-epoxide in the body, which can randomly insert itself into the grooves of DNA.

Once bound in the groove, DNA is not able to be replicated or transcribed effectively.

This may cause mutations in daughter cells or unfavorable effects on gene expression.

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