Can Carbon Monoxide Cause Cancer? Potential Dangers

Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete combustion of carbon-based fuels. While its immediate toxicity is well known, its potential long-term health effects, including cancer risk, remain less understood. Research has investigated whether prolonged exposure to CO triggers biological changes that could contribute to cancer. Understanding these connections requires examining CO’s impact on tissues at a cellular level and reviewing human and animal studies on the subject.

Common Sources of Exposure

Carbon monoxide exposure occurs in various environments, often undetected due to its lack of color and odor. A primary source is incomplete combustion of fossil fuels in homes, workplaces, and outdoor settings. Gas-powered appliances like stoves, furnaces, and water heaters can emit CO if not properly ventilated. Similarly, wood-burning fireplaces and charcoal grills release CO, especially in enclosed or poorly ventilated spaces. The U.S. Consumer Product Safety Commission (CPSC) reports that malfunctioning heating systems are a major cause of CO-related incidents in homes, highlighting the need for regular inspections and proper ventilation.

Motor vehicle exhaust is another significant source, particularly in urban areas with heavy traffic. Internal combustion engines produce CO, and exposure is heightened in enclosed spaces like garages or tunnels. Studies show that people in occupations with prolonged exposure to vehicle emissions, such as toll booth operators, mechanics, and traffic police, may have elevated CO levels in their blood. Research in Environmental Health Perspectives found that urban commuters can inhale substantial CO amounts during peak traffic, sometimes exceeding outdoor ambient levels due to poor air circulation inside vehicles.

Industrial processes also contribute to CO exposure, particularly in manufacturing and metal refining. Workers in steel mills, petroleum refineries, and chemical plants may encounter CO emissions from high-temperature operations. The Occupational Safety and Health Administration (OSHA) sets permissible exposure limits at 50 parts per million (ppm) over an eight-hour work shift, but accidental leaks or poor ventilation can lead to dangerous levels. Research in The Annals of Occupational Hygiene has documented CO poisoning cases in confined industrial spaces, emphasizing the importance of continuous air monitoring.

Cigarette smoke is another source of CO exposure for both smokers and those exposed to secondhand smoke. Tobacco combustion produces CO, which binds to hemoglobin in the blood, reducing oxygen transport. Chronic smokers often have elevated carboxyhemoglobin levels, sometimes reaching 10% or higher, compared to the typical non-smoker range of 1-2%. Research in Tobacco Control indicates that non-smokers exposed to secondhand smoke in enclosed spaces, such as bars or homes with smokers, also experience increased CO levels, raising concerns about long-term health effects.

Biological Effects Leading to Tissue Injury

When CO enters the bloodstream, it binds with hemoglobin to form carboxyhemoglobin (COHb), reducing oxygen transport. This oxygen displacement triggers cellular stress, particularly in high-metabolism tissues like the brain, heart, and kidneys. Hypoxia, or oxygen deprivation, forces cells to shift from aerobic to anaerobic metabolism, leading to lactic acid buildup and a drop in intracellular pH. This metabolic shift disrupts normal cellular function and can induce oxidative stress, where reactive oxygen species (ROS) accumulate and damage proteins, lipids, and DNA.

Oxidative stress extends beyond immediate cellular dysfunction. Studies in Free Radical Biology & Medicine indicate that CO exposure impairs mitochondrial function, leading to energy deficits in affected tissues. Mitochondria, the cell’s primary energy producers, are particularly vulnerable because CO binds to cytochrome c oxidase, a key enzyme in the electron transport chain. This inhibition slows ATP production, pushing cells into a stressed state that may lead to apoptosis or necrosis, depending on exposure severity and duration. In cardiac tissues, this energy deprivation has been linked to myocardial injury, while in neural tissues, prolonged hypoxia may contribute to neurodegeneration.

CO exposure also triggers inflammation. Research in Toxicology and Applied Pharmacology shows that hypoxic stress activates inflammatory pathways, leading to the release of cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These molecules promote endothelial dysfunction, increasing vascular permeability and contributing to tissue edema. In the lungs, prolonged CO exposure has been linked to alveolar damage, particularly in chronic smokers and industrial workers. Persistent inflammation in these tissues can lead to fibrosis, impairing organ function and increasing susceptibility to long-term complications.

Linking Hypoxic Stress to Cancer

Oxygen availability is crucial for cellular stability, and prolonged or intermittent hypoxia from CO exposure can create conditions favorable for tumor development. One key factor is the stabilization of hypoxia-inducible factor 1-alpha (HIF-1α), a transcription factor regulating genes involved in cell survival, angiogenesis, and metabolic reprogramming. Under normal oxygen levels, HIF-1α is rapidly degraded, but when oxygen drops, it accumulates and activates pathways that promote cell proliferation and resistance to apoptosis—hallmarks of cancer progression.

HIF-1α also drives angiogenesis by upregulating vascular endothelial growth factor (VEGF), enabling tumors to sustain growth beyond a few millimeters. Studies in Cancer Research show that chronic hypoxia leads to more aggressive tumor characteristics, with increased vascular density and a higher likelihood of metastasis. In the context of CO exposure, repeated hypoxic episodes could create conditions where pre-malignant cells gain a survival advantage, expanding in an environment that favors glycolytic metabolism over oxidative phosphorylation. This metabolic shift, known as the Warburg effect, has been observed in various cancers and supports rapid cell division.

Beyond metabolic changes, hypoxic stress can induce genetic and epigenetic alterations that contribute to cancer. DNA repair mechanisms may be compromised as oxidative stress accumulates, leading to mutations that disrupt tumor suppressor genes like TP53. Additionally, epigenetic modifications, including DNA methylation and histone acetylation, can silence genes controlling cell cycle regulation and apoptosis. Research in Nature Reviews Cancer highlights how chronic hypoxia leads to widespread epigenetic reprogramming, allowing cells to evade normal regulatory controls and adopt a malignant phenotype. These changes are particularly concerning in tissues experiencing recurrent hypoxic episodes, as seen in individuals with chronic CO exposure from occupational or environmental sources.

Observational Findings From Human Studies

Epidemiological research has explored whether prolonged CO exposure correlates with increased cancer risk, particularly in occupational or environmental settings. While CO itself is not classified as a carcinogen, its role in chronic hypoxia and oxidative stress raises concerns about its contribution to tumor development. Large-scale cohort studies have yielded mixed results, with some suggesting a potential association between long-term exposure and increased cancer incidence, particularly in respiratory and hematologic malignancies.

A study in Environmental Health analyzed cancer rates among workers frequently exposed to CO, such as firefighters, traffic police, and industrial employees. Findings showed a slightly higher prevalence of lung and bladder cancer in these groups compared to the general population, though confounding factors like exposure to other pollutants made it difficult to isolate CO’s role. Similarly, a case-control study in Occupational and Environmental Medicine assessed cancer risk in urban populations exposed to elevated CO from traffic emissions. Results indicated a modest increase in lung cancer incidence, particularly among non-smokers, implicating air pollution as a contributing factor.

Animal Research Insights

Animal studies provide insights into the potential link between CO exposure and cancer. Unlike human research, which relies on observational data, controlled experiments allow precise manipulation of CO concentration and exposure duration. These studies primarily focus on how chronic hypoxia and oxidative stress influence cellular changes that may contribute to tumor formation.

Rodent models have been widely used to assess CO’s impact on organs vulnerable to hypoxic damage. Research in Toxicological Sciences showed that rats exposed to moderate CO levels over several months exhibited increased HIF-1α and VEGF expression in lung tissues, suggesting a shift toward a tumor-promoting environment. Another study found that mice subjected to intermittent CO exposure developed abnormal cell proliferation in bronchial epithelium, a precursor to lung neoplasia. While these studies do not confirm CO as a direct carcinogen, they highlight how prolonged exposure may create conditions that facilitate malignant transformation.

Beyond pulmonary effects, CO exposure has systemic consequences. A study in Carcinogenesis found that mice exposed to CO-enriched environments developed altered liver metabolism, increased lipid peroxidation, and DNA damage in hepatocytes. These findings suggest that CO-induced oxidative stress may affect multiple organs with high metabolic activity. Some research has also examined CO exposure’s impact on hematopoietic cells, revealing disruptions in bone marrow function that could theoretically contribute to leukemia. While definitive links between CO and cancer remain inconclusive, these animal studies reinforce the need for further research into the long-term biological effects of chronic exposure.