Carcinogens

Carcinogens are agents—chemical, physical or biological—that promote the development of cancer by disrupting normal cellular processes and inducing uncontrolled cell growth. These agents operate through a wide range of mechanisms, but most act by damaging DNA or interfering with the systems that maintain genomic integrity. Over time, the accumulation of genetic mutations can disable the regulatory pathways that restrain cell division, ultimately resulting in malignancy.

Mechanisms of Carcinogenic Action

Carcinogenesis is typically a multistep process, during which successive mutations progressively dismantle the checks and balances that govern cell proliferation. When DNA repair mechanisms fail to identify or correct damage, the defective genetic material is passed to daughter cells and accumulates across generations.
Carcinogens can be broadly categorised based on whether they require metabolic activation:

• Activation-dependent carcinogens (indirect-acting)These agents are relatively inert in their parent form. Once absorbed, they undergo metabolic conversion—often in the liver—into reactive intermediates capable of covalently binding to DNA.Examples include:
  • Polycyclic aromatic hydrocarbons (PAHs)
  • Heterocyclic aromatic amines
  • Mycotoxins
• Activation-independent carcinogens (direct-acting)These substances can damage DNA without prior modification. They commonly contain electrophilic groups that readily attack the nucleophilic sites on DNA.Examples include:
  • Ultraviolet radiation
  • Ionising radiation
  • Alkylating agents

The time between exposure and clinical cancer—known as the latency period—varies widely. Solid tumours often develop decades after exposure, with latency commonly spanning 10–40 years. Certain blood cancers may develop within just a few years, complicating efforts to identify specific causative agents.

Classification and Evaluation

Several major organisations evaluate evidence for carcinogenicity:

• International Agency for Research on Cancer (IARC), which classifies substances into:
  • Group 1: Carcinogenic to humans
  • Group 2A: Probably carcinogenic
  • Group 2B: Possibly carcinogenic
  • Group 3: Not classifiable
• Other bodies include:
  • The US National Toxicology Program
  • The National Institute for Occupational Safety and Health (NIOSH)
  • The American Conference of Governmental Industrial Hygienists (ACGIH)

These evaluations draw on epidemiological data, laboratory experiments and mechanistic studies.

Sources of Carcinogen Exposure

Carcinogens originate from a wide array of natural and human-made sources. Common environmental and lifestyle exposures include:

• Ultraviolet radiation from sunlight
• Radon in domestic environments
• Tobacco smoke, containing numerous potent carcinogens
• Environmental pollutants, such as chlordecone
• Alcohol consumption
• Processed meats and high-temperature cooking practices

Occupational settings account for a major proportion of cancers, with estimates suggesting that more than one-third of cases worldwide may be associated with workplace exposures. Well-established examples include:

• Vinyl chloride (linked to liver angiosarcoma)
• Benzene (leukaemia)
• Aniline dyes (bladder cancer)
• Asbestos (mesothelioma)
• PAHs (cancers among chimney sweeps)

Radiation and Carcinogenicity

Ionising radiation, including alpha, beta and gamma emissions, can break chemical bonds and damage DNA directly. The carcinogenic hazard depends on:

• the type of radiation
• the route and duration of exposure
• the energy and penetrating power of the emissions

Alpha particles, though easily stopped externally, are highly carcinogenic when alpha-emitting substances are inhaled or ingested. An example is Thorotrast, a radiographic contrast agent once used clinically, which caused significant internal alpha radiation exposure.
Non-ionising radiation has insufficient energy to break chemical bonds. Radio waves, microwaves and visible light are not considered carcinogenic under normal circumstances. Higher-energy ultraviolet radiation, however, is strongly carcinogenic and the most common cause of skin cancer.
Food irradiation, which uses controlled electromagnetic or electron-based radiation to eliminate pathogens, does not induce carcinogenic changes in the food.

Carcinogens in Foods and Cooking

Several dietary and food-processing factors are associated with cancer risk:

• Alcohol increases the risk of cancers of the head and neck, oesophagus, liver, colon and breast, particularly when combined with tobacco smoking.
• Processed meats contain nitrites and related compounds that can form carcinogenic species under certain conditions.
• High-temperature cooking, such as grilling and barbecuing, produces PAHs and heterocyclic amines, which can bind DNA following metabolic activation.
• Acrylamide, formed during high-temperature cooking of starchy foods, prompted concern in the early 2000s, although subsequent evidence suggests that typical dietary intake does not significantly increase cancer risk.

Biological Carcinogens

Numerous biological organisms contribute to carcinogenesis, often through chronic infection or toxin production. Examples include:

• Aflatoxin B₁ from Aspergillus flavus, a major cause of hepatocellular carcinoma
• Helicobacter pylori, implicated in stomach cancer and MALT lymphoma
• Hepatitis B and C viruses, associated with liver cancer
• Human papillomavirus (HPV), the principal cause of cervical cancer

Tobacco Smoke

Cigarette smoke contains at least seventy known carcinogens, including PAHs, benzene and nitrosamines. Tobacco use is linked to a wide range of cancers, such as those of the lung, larynx, stomach, kidney, pancreas, liver, bladder, cervix and colon, as well as haematological malignancies.

Occupational Carcinogens

Workers in specific industries may experience sustained exposure to hazardous substances, providing much of the historical evidence for carcinogenicity. Examples of occupational carcinogens include:

• By-products of metal refining
• Chemicals used in semiconductor and electronics manufacture
• Certain medications and agricultural chemicals
• Contaminants in groundwater
• Asbestos fibres, historically used in construction and insulation