Tumor Etiology and Historical Examples
The development of malignant neoplasms is always associated with damage to the cellular apparatus. Carcinogenic agents target the cellular genome. As a result of this exposure, a fatal error occurs: the normal genetic life program is completely replaced by a pathological tumor formation program. This process is called malignant transformation.
By origin, all carcinogenic factors are divided into three main groups: chemical, physical, and biological (the latter include oncogenic viruses). A critical risk factor that significantly increases the body's susceptibility to carcinogens is the presence of various genetic defects.
Many chemical substances can trigger malignant transformation under specific conditions, including certain medications. Historically, the harmful effects of chemical compounds were recognized by physicians long before detailed studies of DNA. Classic clinical examples include:
- Soot (coal combustion byproducts): contact caused occupational scrotal cancer in chimney sweeps (described by Pott in 1775).
- Asbestos dust: inhalation specifically damages respiratory tract tissues, causing pleural mesothelioma.
- Tobacco smoke combustion products: a proven cause of lung cancer.
Classification by Chemical Structure
Chemical carcinogens are traditionally divided into two large groups: organic and inorganic compounds.
1. Organic Compounds This is the largest group, encompassing several classes of substances with entirely different mechanisms of action:
- Polycyclic Aromatic Hydrocarbons (PAHs): exhibit pronounced local action, meaning they induce tumor development directly at the site of tissue contact. 3,4-Benzpyrene has the highest carcinogenic activity, along with 20-methylcholanthrene and dimethylbenzanthracene. Major sources of PAHs include tobacco smoke, automobile exhaust, and smoked foods.
- Aromatic Amines and Amides: unlike PAHs, these act via resorptive action. They become active only after absorption into the bloodstream, causing tumors at a distance from the initial site of entry. Notable examples include 2-naphthylamine, benzidine, and 2-aminofluorene. Important feature: 2-naphthylamine, benzidine, and 2-aminodiphenyl exhibit strict organ specificity, causing urinary bladder cancer.
- Nitroso Compounds: include some of the most dangerous substances for humans (diethylnitrosamine, dimethylnitrosamine, and nitrosomethylurea).
- Aminoazo Compounds: possess potent carcinogenic properties (4-dimethylaminoazobenzene, o-aminoazotoluene).
- Aflatoxins: chemically derived from coumarins. These are toxic metabolic products of mold fungi, predominantly Aspergillus flavus.
- Heterocyclic Aromatic Hydrocarbons: represented by dibenzacridine and dibenzcarbazole.
- Other Organic Substances: epoxides, various plastics, urethane, carbon tetrachloride, and chloroethylamines.
2. Inorganic Compounds Inorganic chemical carcinogens include heavy metals and their derivatives: arsenic, beryllium oxide, chromates, and cobalt.
Classification by Origin
Depending on the source of the carcinogenic substances within the body, they are classified into two groups: exogenous and endogenous.
Exogenous Chemical Carcinogens These are substances that enter the body exclusively from the external environment. This group includes asbestos, as well as inorganic compounds: chromates, arsenic and its compounds, cobalt, and beryllium oxide.
Endogenous Carcinogens These compounds do not come from outside sources but are formed directly within the body. Their formation is linked to the physicochemical modification of normal metabolic products. Potential endogenous carcinogens include:
- Hormones (specifically estrogens).
- Bile acids.
- Certain amino acids (tyrosine, tryptophan).
- Lipid peroxidation products.