Air Pollution: Mutations And Health Hazards

Air pollution is a pervasive issue in urban and industrial areas, and evidence suggests that it can have detrimental effects on human health and fertility. Studies have found a link between air pollution and DNA mutations, particularly in male germ cells and sperm. Sentinel animal studies have shown that exposure to polluted air can lead to an increased mutation rate in mice, with DNA in the sperm of these mice containing up to 60% more mutations than those breathing filtered air. This raises concerns about the potential impact of air pollution on human germline mutation rates and the risk of genetic conditions. While the specific mechanisms by which air pollution causes DNA damage are not yet fully understood, it is clear that air pollution can have significant genotoxic effects, and further research is needed to determine the extent of the risk to humans.

Air pollution and DNA methylation

Air pollution is known to be harmful to health, and emerging data suggests that exposure to air pollution may contribute to the development of lung conditions, metabolic disorders, and cardiovascular disease. While the acute effects of exposure to air pollutants are known, the impact of exposures during gestation or childhood on disease development is not yet clear.

Several traffic-related air pollution (TRAP) components have been associated with changes in DNA methylation (DNAm). These include particulate matter (PM), black carbon (BC), ozone (O3), nitrogen oxides (NOx), and polyaromatic hydrocarbons (PAHs). Typically, exposure to these pollutants leads to a decrease in DNAm.

DNAm describes the attachment of methyl groups to DNA, usually at the fifth carbon of cytosines, leading to the formation of 5-methylcytosine (5-mC). In mammals, DNAm predominantly occurs at C-G dinucleotides. Ten-eleven translocation methylcytosine dioxygenase (TET) family members can catalyze DNA demethylation through the conversion of 5-mC to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxycyotosine (5-caC). Air pollution-induced reactive oxygen species (ROS) may increase the oxidation of 5-mC to 5-hmC. Global generation of 5-mC may also be decreased by air pollution-induced reductions in DNA methyltransferase (DNMT) expression.

Studies have found associations between prenatal exposure to air pollution and newborn DNA methylation. Six CpGs were significantly associated with lung function and asthma. Long-term exposure to air pollution has also been linked to DNA methylation and lung function in adults. The LifeLines Cohort Study found significant associations between exposure to nitrogen dioxide and DNA methylation in whole blood.

While the exact mechanisms are not yet fully understood, air pollution exposure is estimated to contribute to approximately seven million early deaths every year worldwide and more than 3% of disability-adjusted life years lost. Further research is needed to fully understand the health impacts of air pollution and to identify ways to mitigate its harmful effects.

Industrial air pollution and mutations

Industrial air pollution is a pressing issue that has the potential to affect many people in most countries. Integrated steel production, for example, generates chemical pollution containing compounds that can induce genetic damage. Investigations of herring gulls in the Great Lakes demonstrated elevated DNA mutation rates near steel mills, indicating the presence of mutagenic compounds in the air.

To study the impact of industrial air pollution on mutations, scientists have conducted experiments using laboratory mice. In one study, groups of mice were exposed to ambient air in polluted industrial areas near steel mills. The results showed a significant increase in heritable mutation frequency at tandem-repeat DNA loci, with a particular impact on the paternal germline. This increase was compared to a reference site located further away from the industrial area. The industrial site was chosen due to its high levels of chemical mutagens, such as polycyclic aromatic hydrocarbons (PAHs), which are produced by integrated steel mills and are among the most genotoxic components of urban air pollution.

The use of sentinel laboratory animals, or "sentinel animal studies," is a powerful approach for assessing the hazards of industrial air pollution. These studies have provided evidence that ambient air pollution may increase human germline mutation rates, especially at repetitive DNA loci. While the causative agents and mechanisms are still being investigated, there is a growing body of evidence linking air pollution exposure to DNA damage in human sperm, suggesting that our germ cells are vulnerable to the genotoxic effects of industrial air pollution.

The potential consequences of industrial air pollution on human health are severe. Exposure to air pollution has been linked to various somatic cell endpoints, including cancer. While the impact on human germline mutations is not yet fully understood, the available data suggests that industrial air pollution can increase the risk of mutations in humans, particularly in those living or working in close proximity to industrial areas. Therefore, there is an urgent need to identify and restrict the release of important chemical mutagens, as well as to further investigate the genetic consequences associated with exposure to industrial air pollution.

Germline mutations

Several studies have investigated the link between air pollution and germline mutations. While the potential for inducing mutations in the human germline remains unclear, animal studies have provided proof of principle that ambient air pollution can induce germline mutations in vertebrates such as birds and mice.

One study exposed laboratory mice to ambient air in a polluted industrial area near steel mills. The results showed that the heritable mutation frequency at tandem-repeat DNA loci in these mice was 1.5 to 2.0 times higher than those at a reference site 30 km away. This increase in mutations was primarily due to an increase in mutations inherited through the paternal germline. Another study found that offspring born from male mice exposed to industrial air pollution had twice the mutation rate as those whose fathers breathed rural or filtered polluted air. The likely cause is small particles that can carry known mutation-causing compounds, such as polycyclic aromatic hydrocarbons, deep into the lungs.

In addition to animal studies, some human studies have also suggested a possible link between air pollution and germline mutations. Several recent studies have linked air pollution exposure to DNA damage in human sperm, indicating that human germ cells are susceptible to the genotoxic effects of air pollution. Furthermore, investigations of herring gulls nesting near steel mills on the Great Lakes showed higher germline mutation rates at minisatellite DNA loci than those at rural sites, and the mutation frequency increased with proximity to the steel mills. While other factors such as nutritional status and disease burden could not be eliminated as contributing factors, the results suggest that inhaled airborne contaminants emitted from steel mills may play a significant role in mutation induction.

While direct ESTR mutation induction in the female germline by any mutagen has not been investigated, indirect maternal ESTR mutation induction has been observed. The effects of long-term, low-dose exposure of adults and embryonic exposures during gametogenesis on female germline mutations are areas that require further research.

Airborne pollutants in utero

Airborne pollutants have been shown to cause several health issues in individuals exposed to them in utero. These health issues include respiratory, circulatory, neoplasms, mental health, and nervous system conditions. A study that used the Great London Smog (GLS) of 1952 as a quasi-natural experiment found that individuals exposed to the GLS in utero had a 2.58% increase in the probability of at least one respiratory health-related hospitalization between 1997 and 2020, relative to the sample mean. This equates to a 23% increase.

The effects of airborne pollutants on individuals exposed to them in utero are not limited to physical health issues. Empirical analyses have shown that such individuals have worse health outcomes during childhood. However, there is little evidence on the long-term health impacts of exposure to airborne pollutants in utero.

Studies have also shown that persistent organic pollutants (POPs) can pass through the placental barrier and enter the fetal bloodstream. POPs have been found in all cord blood samples collected during a study in Singapore in 2006. Chlordanes and polychlorinated biphenyls (PCBs) were observed to have adverse effects on fetal growth (birth weight, length, and head circumference) and health.

In a study on mice, pregnant mice were exposed to an atmosphere representative of a 2017 pollution event in Beijing, China. The study found that in utero exposure to air pollution disturbed the offspring's gut maturation and microbiota during the intestinal suckling-to-weaning transition in a sex-dependent manner. In utero exposed male mice exhibited decreased villus and crypt length, vacuolation abnormalities, and lower levels of tight junction protein ZO-1 in the ileum. They also showed an upregulation of absorptive cell markers and a downregulation of neonatal markers in the colon. The cecum of in utero exposed male mice also presented an unbalanced inflammatory pattern. In utero exposed female mice displayed less severe intestinal alterations, but still included dysregulated expression of Lgr5 in the colon, Tjp1 in the cecum, and Epcam, Car2, and Sis in the ileum.

Air pollution and sperm mutations

Air pollution is a common issue in all countries, and it can have a significant impact on reproductive functions in both men and women. It is known to particularly affect sperm parameters in men. A meta-analysis of 11 articles published between 1978 and 2013 revealed that air pollution reduces sperm motility and can contribute to male infertility.

Several studies have found a link between exposure to air pollution and alterations in sperm parameters, including decreased sperm motility, morphology, and count. For example, a study of toll collectors working at motorways found that exposure to diesel exhaust had detrimental effects on semen parameters. Another study of healthy young men exposed to air pollution found an association with sperm aneuploidy, which is an abnormal number of chromosomes.

The impact of air pollution on sperm quality is of great interest and priority for scientists and governmental institutions, as it can provide valuable information for developing solutions to remove contaminants harmful to sperm parameters and reducing infertility rates. It is also important to consider the potential impact on the offspring of those exposed to air pollution, as there may be a risk of heritable mutations.

While the specific mechanisms are not yet fully understood, it is believed that air pollution may cause sperm mutations through DNA damage and methylation. Studies in mice have shown that breathing polluted air can lead to increased DNA breakage and methylation, which can affect gene expression and function in offspring. Additionally, particulate matter in the respirable range (PM 2.5) and polycyclic aromatic hydrocarbons (PAHs) found in air pollution are known to be associated with sperm alterations and DNA damage.

Overall, while more research is needed to fully understand the relationship between air pollution and sperm mutations, the current evidence suggests that air pollution can have detrimental effects on sperm quality and may increase the risk of mutations in offspring.

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