Carcinogens

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Overview


Carcinogens are substances, whether chemical or physical, that cause cancer. Cancer is the uncontrolled division and growth of cells; these cells can spread and invade surrounding tissues, replacing normal cells.

Humans can be exposed to carcinogens when they are present in food, air, or water. In addition, some carcinogens are created within the body as products of metabolism or certain pathophysiologic states like inflammation or oxidative stress. Carcinogens from the environment likely contribute to a large percent, possibly the majority, of human cancers when related to lifestyle, including diet and tobacco use.

Tumors are tissues that grow more rapidly than the surrounding tissue and form an enlarged mass of cells. Tumors can be either benign or malignant. Benign tumors are often encapsulated and grow slowly; they do not metastasize, and rarely exhibit anaplasia, the loss of cellular differentiation and function. Malignant tumors are not encapsulated, and they grow quickly and metastasize into the surrounding tissues. Metastasis is the ability of tumor cells to break free of the tumor and enter the bloodstream, where they travel to other parts of the body and begin to grow. They display anaplasia and are poorly differentiated.

(#Wogan 2004), (#Kent 1998)

Mechanism of Action


Some toxic Chemicals List directly affect DNA or DNA replication, and are known as genotoxic carcinogens.

Tumor Development and Growth


The development and growth of tumors proceeds in three stages.

1. Initiation Stage
In this stage, DNA is irreversibly changed by genotoxic agents called initiators. DNA damage to a cell most frequently results in cell death, but sometimes DNA mutation creates rapidly dividing cells. Cell division is normally limited by cell-to-cell contact, but cancercells have lost this ability to control cell division.

Initiating carcinogens include:

Other agents created endogenously within the body can also be considered initiating factors.


2. Promotion Stage
Tumors are considered to be in the promotion stage when they continue growth without stimulation from a carcinogen-DNA interaction. Promotion can be an increased expression of the altered DNA formed in the initiation stage, but can occur without DNA involvement. The carcinogen that caused the initiation stage may or may not be the toxin driving the promotion stage.

Promotion can be stopped through removal of the promoter carcinogen, while the initiation stage cannot be reversed.

3. Progression
In this stage, cells rapidly divide, normal tissue is invaded by cancerous cells, metastasis increases, and cells lose differentiation. Progression is similar to initiation in that both are irreversible. In this stage, the cells are not affected by removing the carcinogen.

Progressor agents are those toxins which cause a transition from the promotion to progression stage. Often, progressor agents inhibit DNA repair.

Progressor agents include:

A complete carcinogen is a toxin capable of triggering all three stages of tumor progression (#Kent 1998).


International Agency for Research on Cancer (World Health Organization): Monographs on the Evaluation of Carcinogenic Risks to Humans

Collaborative on Health and the Environment: Toxicant and Disease Database

References


Kent C. 1998. Basics of Toxicology. New York, NY:John Wiley & Sons, Inc.

Oliveira PA, Colaço A, Chaves R, Guedes-Pinto H, De-La-Cruz P LF, Lopes C. 2007. Chemical Carcinogenesis. An Acad Bras Cienc. 79(4):593-616.

Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. 2004. Environmental and chemical carcinogenesis. Semin Cancer Biol. 14(6):473-86.

Sarasin A. 2003. An Overview of the Mechanisms of Mutagenesis and Carcinogenesis. Mutat Res. 544(2-3):99-106.

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