One life-threatening response to chemicals is the development of cancer.  While not all toxicants are carcinogens, many may either directly cause the abnormal growth of cells or enhance the cancer-causing effects of other chemicals.

Definitions:

Tumour -- hyperplasia or abnormal growth of cells.  Tumours may be either benign (localised, self-contained) or malignant (capable of spreading).

Carcinoma -- a malignant tumour of epithelial origin

Sarcoma -- a malignant tumour of connective tissue origin

Direct interaction with the DNA or RNA, which results in changes that are heritable from cell line to cell line.

Interference with enzymes that control DNA repair, replication, or transcription.

Interference with normal control mechanisms such as the histone that may contribute to DNA replication/synthesis.

Genotoxic carcinogens are those that have direct interaction with DNA/RNA.  These are further classified as
Direct (Primary) carcinogens -- agents that interact with DNA themselves in a true nucleophilic/electrophilic reaction.  Direct carcinogens may be organic or inorganic (e.g. chromium) in nature.

Pro-carcinogens (Secondary carcinogens) -- agents that must be bio-activated to a carcinogen that then interacts directly with DNA   An example of an pro-carcinogen is aflatoxin B1 which is hepatically metabolised to an epoxide intermediary that may interact with nucleic acids, thus causing liver cancer.

Indirect carcinogens -- some compounds may interfere with DNA by disturbing or disrupting DNA function or repair, i.e. by altering DNA polymerase function (such as nickel).
 

Epigenetic carcinogens -- agents that cause cancer by some indirect mechanism that either alters DNA or allows overgrowth of transformed cells.
Solid state carcinogens -- Asbestos is the classic example of this type of carcinogen.  It does not directly cause DNA damage.  However, when deposited on the pulmonary epithelia, it is treated as a foreign substance.  As phagocytosis and repair occur, the shape of the fibre interferes with normal repair cell growth, causing mutations that are incorporated into the cell line, hence overgrowth of transformed cells.

Hormones -- Diethylstilboestrol, oestrogen, and testosterone will promote the growth of hormone-dependent cells in cancers of the cervix, breast, and prostate respectively.  Again, these agents do not cause the transformation but do promote its growth.

Immunosuppressants -- drugs and toxicants that depress the immune system will consequently allow the overgrowth of any foreign organisms.   Some cancers may be spurred to growth by viral infections that inhibit normal DNA function.  Hence, the immunosuppressant allowed the growth of the virus, which allowed expression of the cancer.  Immunosuppressant-induced decreases in killer cell activity will also contribute to the proliferation of atypical cells.
 

Co-Carcinogens are chemicals that, alone, do not cause cancer.  However in the presence of other chemicals, they may exert carcinogenic activity.  Ethanol is an example of a co-carcinogen.  Co-carcinogens may also greatly increase the risk of true carcinogens when exposure to both occurs.

Promotors -- are agents that, again, are not carcinogenic.  However, they will allow a co-carcinogen to exert its cancerous effects.  Classic examples of promotors include phorbol ester and croton oil.  Exposure to either (alone or together) will not cause cancer.  However, either agent with ethanol, will allow the ethanol to be carcinogenic.  The agents promote the carcinogenic effect of co-carcinogens.  Note that promotion may occur following exposure to the carcinogen or co-carcinogen.  (Exposure to the co-carcinogen results in altered DNA and the potential for cancer.  Subsequent exposure, even weeks, months, or years later, to a promotor allows expression of the cancer.)

Direct Chemical Interaction with DNA (Carcinogens or Activated Pro-carcinogens)
Bases in DNA are nucleophiles and as such are strongly attracted to electrophilic compounds. Many (but not all) carcinogens are electrophilic.  Carcinogens such as epoxides, nitrogen mustards, nitrosoureas, and nitrosamines may all act in this fashion.  Additionally, pro-carcinogens such as polycyclic aromatic hydrocarbons, aromatic amines, mycotoxins (including aflatoxin), and, again, nitrosamines, may also act by this mechanism.  This interaction will result in several types of damage to the DNA, such as alkylated bases (carcinogens that are alkylating compounds) in which side chains have been added to the base that interferes with DNA replication and/or transcription.

Indirect chemical interference with DNA may occur with anti-metabolites such as the purine and pyrimidine analogues.  These agents inhibit the synthesis of purine or pyrimidine bases and therefore inhibit the synthesis of DNA.

Intercalating agents interpose between the strands within the grove of DNA, thereby inhibiting its replication/transcription.  The anti-neoplastic antibiotics daunomycin (daunorubicin), doxorubicin (doxomycin) and actinomycin D are examples of intercalating agents.

Interference with enzyme control or enzyme repair mechanisms such as nickel-induced inhibition of  DNA polymerase, as previously described, which may result in missing bases or improperly linked base pairs.

Damage to the histone, which may allow unregulated or improperly controlled DNA replication.

IRRITATION, that is the first step in the development of cancer.  Following the irritation, the damage must be expressed.

PROMOTION, or expression of the damaged DNA, is the second step in carcinogenesis.  Since these cells are now atypical (transformed) the cells will proliferate.

OVERGROWTH of the cancerous cells refers to the full expression of cancer, that occurs with cellular proliferation.  If other tissues become involved, the cancer has reached the next stage of development.

METASTASIS refers to the spread of cancerous cells to other tissues.  For example a cancer that originated in the breast may metastasise to the liver.  This typically occurs by one or more of three physiologic mechanisms.

Physical growth into a neighboring organ (from stomach to liver, pancreas to stomach, et c.)

Cancerous cells separate from the original growth and

become blood- or lymph-borne, carried to other tissues where they attach and begin a new area of abnormal growth or

simply "drop-off" one organ and become associated with another (i.e. cells dissociate from a cancerous liver, are "loose" in the abdominal cavity and find their way and attach to the kidney).

Multiple exposure -- Exposure more than once to a particular carcinogen OR exposure to more than one carcinogen, pro-carcinogen, co-carcinogen, or promotor, will increase the risk of cancer.

Viral infection -- As previously described, chronic viral infection may predispose the subject to the development of certain forms of cancer.

Immunologic status -- As previously described, immunodepression may increase viral and/or bacterial growth, that could increase the risk of cancer.

Diet -- A number of dietary factors may influence the development of cancer.

High fat diet -- increased risk (especially brown fat, including high body levels of brown fat)
Malnutrition -- with compromised stress response may predispose to cancer
Protein free diet -- decreased risk of cancer, probably due to exposure to fewer carcinogens (PAHs)
Anti-oxidant supplementation -- evidence supports studies which indicate that sensible anti-oxidant (selenium, ascorbic acid, alpha-tocopherol) supplementation does decrease the risk of certain cancers.