Chemical carcinogens, chemoprevention and aflatoxin

How chemicals cause cancer, how agencies rank carcinogens, and how drugs and public health measures can prevent some cancers.

Updated Nov 12, 2026

Chemical carcinogenesis is a multistep process: a chemical, often after being activated by the body's own enzymes, damages DNA (initiation), and other signals push the damaged cell to multiply (promotion). Chemoprevention means using drugs to interrupt that process before cancer appears. Aflatoxin, a mould toxin in stored grains and nuts, is a classic example of both, and is relevant in tropical Latin America.

Key points

IARC groups agents by the strength of evidence that they can cause cancer: group 1 (carcinogenic), 2A (probably), 2B (possibly) and 3 (not classifiable); this is hazard, not risk.
Genotoxic carcinogens damage DNA, often after CYP enzymes turn them into reactive metabolites; nongenotoxic carcinogens drive proliferation, often through receptors.
Initiation is a heritable DNA change; promotion makes initiated cells multiply; complete carcinogens do both.
Chemoprevention can block carcinogen activation, boost detoxification, reduce inflammation or act on hormone receptors; tamoxifen and raloxifene are approved to reduce breast cancer risk in high-risk women.
Aflatoxin B1 from Aspergillus flavus is activated by CYPs to an epoxide that binds guanine and causes a typical TP53 mutation; with hepatitis B it greatly raises liver cancer risk.
Several attractive chemopreventive candidates failed or caused harm in trials, so prevention claims need proof from randomized studies.

How carcinogens are classified

IARC, WHO's cancer agency, weighs human, animal and mechanistic evidence. Group 1 agents are carcinogenic to humans (for example asbestos, aflatoxin B1, TCDD, beryllium and cadmium); group 2A are probably carcinogenic (glyphosate since 2015); group 2B possibly; group 3 not classifiable. The classification reflects how strong the evidence is that an agent can cause cancer, not how likely cancer is at a given exposure; risk depends on the dose and duration of exposure.

Genotoxic and nongenotoxic carcinogens

Genotoxic carcinogens form DNA adducts or reactive oxygen species. Many are procarcinogens that CYP enzymes activate in the target tissue: benzo[a]pyrene from tobacco smoke and aflatoxin B1 (which becomes an 8,9-epoxide) are examples.
If DNA damage is not repaired before the cell divides, it becomes a permanent mutation; mutations in oncogenes or tumour suppressor genes initiate a tumour.
Nongenotoxic carcinogens raise cancer rates without damaging DNA directly, often by activating receptors that drive proliferation and survival; TCDD acting through the aryl hydrocarbon receptor and the phorbol esters are examples.
Cocarcinogens increase the effect of another carcinogen, for example by aiding its absorption or activation or by interfering with DNA repair; asbestos and smoking together multiply lung cancer risk.

Initiation, promotion and progression

A single initiated cell is not yet a cancer. Promoters, such as inflammation, hormones or receptor-activating chemicals, make initiated cells multiply, and further changes lead to invasion and metastasis. Some chemicals are complete carcinogens: repeated exposure both initiates and promotes. Because promotion takes many steps over years, drugs that block it are attractive for prevention.

Chemoprevention

Blocking activation or boosting detoxification: isothiocyanates and drugs such as oltipraz inhibit CYPs and induce glutathione and other detoxifying enzymes through the antioxidant response element.
Trapping carcinogens: chlorophyll and related compounds can bind carcinogens or their metabolites before they reach DNA.
Anti-inflammatory: long-term aspirin reduces colorectal adenomas; celecoxib also did, but its cardiovascular risk stopped the trial.
Hormone receptors: tamoxifen and raloxifene are approved to lower the risk of invasive breast cancer in high-risk women, raloxifene also in postmenopausal osteoporosis; raloxifene carries a boxed warning for venous thromboembolism and stroke death.
Cautionary results: retinoids increased lung cancer in large trials, and alpha-tocopherol (vitamin E) increased prostate cancer; most candidates tested so far have shown no benefit.
Vaccines against hepatitis B and HPV prevent cancers by preventing the infections that cause them, rather than by acting on chemical carcinogenesis.

Aflatoxin B1

Aflatoxins are made by Aspergillus flavus on maize, peanuts, cottonseed and tree nuts stored in hot, humid conditions, so exposure is a problem in tropical regions of Latin America, Africa and Southeast Asia. Aflatoxin B1 is absorbed from the gut and activated in the liver by CYP1A2 and CYP3A4 to an 8,9-epoxide that binds the N7 position of guanine; the resulting G to T change in codon 249 of TP53 is a fingerprint of aflatoxin-related liver cancer. Detoxification products, such as aflatoxin M1, appear in urine and milk. High doses cause acute liver necrosis; chronic exposure causes cirrhosis, immunosuppression and hepatocellular carcinoma. Hepatitis B and aflatoxin act together: the viral HBx protein inhibits p53 and DNA repair, so people exposed to both have a far higher liver cancer risk than with either alone. Prevention combines reducing mould contamination of stored foods, hepatitis B vaccination and, experimentally, chemopreventive drugs such as oltipraz.

Prevention through policy: asbestos in Colombia

WHO assesses all forms of asbestos as carcinogenic and estimates more than 200,000 deaths a year from occupational exposure; it recommends stopping the use of all forms as the most efficient prevention. Colombia's Law 1968 of 2019 prohibits the mining, production, sale, import, distribution and export of any type of asbestos from 1 January 2021, and created health follow-up for exposed workers.

Test yourself

Think of the answer, then tap the question to see it.

What is the difference between a genotoxic and a nongenotoxic carcinogen?

A genotoxic carcinogen damages DNA, often after metabolic activation; a nongenotoxic one raises cancer rates without direct DNA damage, often by driving proliferation through receptors.

Does an IARC group 1 classification mean that any exposure is likely to cause cancer?

No. It means the evidence that the agent can cause cancer is strong; the actual risk depends on the dose, duration and route of exposure.

How does aflatoxin B1 damage DNA?

Liver CYP1A2 and CYP3A4 convert it to an 8,9-epoxide that binds guanine, causing G to T mutations such as the typical one in codon 249 of TP53.

Why does hepatitis B increase the cancer risk from aflatoxin so much?

The viral HBx protein inhibits p53 and DNA repair, the virus alters aflatoxin metabolism and the liver regenerates constantly, so adducts turn into mutations more easily.

Which approved drugs lower the risk of invasive breast cancer in high-risk women?

The selective oestrogen receptor modulators tamoxifen and raloxifene; raloxifene carries a boxed warning for venous thromboembolism.

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Connections

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Asbestos (World Health Organization, 2026); Ley 1968 de 2019, por el cual se prohíbe el uso de asbesto en el territorio nacional y se establecen garantías de protección a la salud de los colombianos (Ministerio de Salud y Protección Social (Colombia), 2019); DailyMed - RALOXIFENE HYDROCHLORIDE- raloxifene tablet (DailyMed (U.S. National Library of Medicine), 2026).

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