Wednesday, October 15, 2008

Neoplasms: Excerpt 6

Neoplasms: principles of development and diversity was published October 1, 2008. In the next few blogs, I will provide some short excerpts from the book.

Excerpt from Chapter 2 Section 2.13. Why Do Chemical Carcinogens Need to be Activated by Cells in our Bodies Before They Can Cause Cancer?

The active moieties of most chemical carcinogens will react with virtually any molecule in their vicinity: air, water, cell membrane, proteins, cytoplasm, or anything. For this reason, chemicals that are chemically reactive in their natural state are almost never carcinogens: they expend all their reactivity on nongenetic molecules before reaching the nucleus! A potent carcinogen is a molecule that can pass through membranes and through the interior of a cell without reacting with other molecules. An effective carcinogen waits until it gets near to its target molecule (DNA) before it activates. In most cases, activation is achieved within the smooth endoplasmic reticulum. In the endoplasmic reticulum are a variety of enzymes that can activate some molecules and deactivate others. Carcinogens are activated to a highly reactive species. Reactive species formed deep within a cell may find their way to DNA. Some of the DNA alterations may lead to mutations that are passed to progeny cells. Some of those mutations may lead to cancer.

There are exceptions. Some unstable molecules spontaneously achieve an active state (without the participation of cellular enzymes), but the rate at which the reactive species are generated is sufficiently slow to give the nonreactive form enough time to gain proximity to the nucleus. This is the case for several carcinogenic alkylating agents.

Other agents produce mutations in DNA without chemically reacting with bases. Intercalating agents (such as ethidium bromide) are examples of carcinogens that are not activated within cells. Silicates and so-called foreign body carcinogens and a range of inert fibers (including asbestos) do not require enzymatic activation. Still, most of the carcinogens delivered in food, air, and water are chemical carcinogens that require intracellular activation.

(to be continued)

The full table of contents is available. In the next few days, I will continue to discuss content from Neoplasms in my blogs.

-Jules Berman

Key words: tumors, tumour, neoplasms, neoplasia, carcinogenesis, tumor development, cancer research, neoplastic development, precancer preneoplasia, preneoplastic

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