DNA damage to oral cells similar in never smoking vapers and current smokers

15th March 2023

DNA damage within oral epithelial cells appears to be similar among vapers who have never smoked and current exclusive smokers

The DNA damage from vaping among individuals who have never smoked is comparable to that induced from current smoking and increases in a dose-dependent manner according to the findings of a study by a team from the Department of Population and Public Health Sciences, University of Southern California, USA.

In a 2021 Cochrane systematic review on the use of electronic cigarettes (otherwise known as ‘vaping’), researchers concluded that there did not appear to be any clear evidence of harm from nicotine electronic cigarettes, but added how the longest follow-up was two years and the overall number of studies was small. However, there does has been an increase in both hospitalisations and death due to what has been termed ‘vaping use-associated lung injury’ which is likely to be the result to cytotoxicity and neutrophilic inflammation caused by inhaled chemicals although further details remain unknown. Much of the harm associated with smoking has been linked to DNA damage due to reactive oxygen and nitrogen species. Consequently, a quantitative assessment of the extent to which such DNA damage occurs, could therefore be used to determine the relative damage caused through vaping and smoking.

In the current study, the US researchers explored the DNA-damaging effect induced by vaping and smoking compared to a group of non-smokers. The team quantified the DNA damage within oral epithelial cells using a polymerase chain reaction assay. The three groups were: exclusive vapers (who had never smoked); exclusive current smokers and non-smokers.

DNA damage in vapers and current smokers

A total of 72 individuals ranging in age from 24.3 to 26 years were included, 24 in each of the three groups.

Mean levels of DNA damage in oral epithelial cells were found to be 2.6- and 2.2-fold higher among vapers and smokers compared to non-smokers (p = 0.005 and 0.02) respectively. In addition, the level of damage was not significantly different between vapers and smokers with the extent of damage increasing in a dose-dependent manner from light to heavy users. Interestingly, the amount of nicotine present in those using electronic cigarettes did not correlate with the level of DNA damage. However, the damage was highest among those using used sweet-, mint or menthol-, and fruit-flavoured e-liquids, respectively.

The authors concluded that their findings had significant implications for public health given how the electronic cigarette flavoured liquids exhibiting the highest damage were also the most popular among younger vapers.

Citation
Tommasi S et al. Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users. Nicotine Tob Res 2023

Glyphosate use associated with elevated biomarkers of oxidative DNA damage

26th January 2023

Glyphosate is a commonly used herbicides and a study in farmers observed positive associations with biomarkers of oxidative DNA damage

Regular use of the herbicide glyphosate among farmers is associated with higher urinary levels of oxidative stress biomarkers, a key characteristic of carcinogens, according to US researchers.

Glyphosate appears to be one of the most widely used herbicides across the world. However, in 2015, the International Agency for Research on Cancer, deemed glyphosate as ‘probably carcinogenic to humans’ based on sufficient evidence derived from animal studies. Despite this assertion, the evidence derived from human studies is mixed. For example, a 2016 systemic review was unable to detect a causal relationship between use of the herbicide and lymphohematopoietic cancer. In contrast, a more recent, 2019 meta-analysis concluded that the findings from both experimental and mechanistic studies suggested a compelling link between the use of glyphosate-based herbicides and non-Hodgkin lymphoma. Moreover, while several in vitro studies indicate the the toxicological effects of glyphosate may occur through the induction of oxidative stress, the evidence from actual human studies is limited.

In the present study, the US team matched US farmers who self-reported use of glyphosate with non-farmers, with no history of cancer of exposure to pesticides within the last 10 years. Enrolled participates provided a first morning urine sample and were asked about use of specific pesticides in the last 12 months. Urinary concentrations of glyphosate and three oxidative stress biomarkers, 8-OHdG, 8-isoprostane and MDA were made and regression analysis performed after adjustments for age, lifestyle and medical factors.

Glyphosate and relationship with oxidative stress biomarkers

A total of 268 males with a mean age of 63.4 (100 of whom served as non-farming controls) were included in the analysis.

The highest quartile of glyphosate urinary concentration was significantly associated with the highest levels of 8-OHdG (geometric mean ratio, GMR = 1.15, 95% CI 1.03 – 1.28) and for MDA (GMR = 1.20, 95% CI 1.03 – 1.40) but not for 8-isoprostane.

Among farmers exposed to the herbicide within 1 day (compared to 5 to 7 days) of urine collection, there was also an association with both 8-OHdG (GMR = 1.20, 95% CI 1.01 – 1.42) and MDA (GMR = 1.28).

The authors suggested that since 8-OHdG reflects oxidative stress-induced DNA damage, their findings support the genotoxic potential of the herbicide.

They concluded that these findings may inform evaluations of the carcinogenic potential of the herbicide.

Citation
Chang VC et al. Glyphosate Exposure and Urinary Oxidative Stress Biomarkers in the Agricultural Health Study. J Natl Cancer Inst 2023.

Study provides insight into how aerobic exercise might reduce colon cancer cell proliferation

13th April 2022

Aerobic exercise induces interleukin-6 and suppresses a marker of DNA damage, offering insight as to how it could reduce the risk of colon cancer

Aerobic exercise increases expression of interleukin-6 (IL-6) and suppresses the level of γ-H2AX, a marker for DNA damage, in a colon cancer cell line, providing a possible explanation as to how exercise reduces the risk of colon cancer. This was the conclusion of a study by a team from the School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle upon Tyne, UK.

In 2020, globally, colon cancer was responsible for over 1.9 million cases and 0.9 million deaths. Moreover, there is evidence that physical activity reduces cancer risk and in 2018, the American physical activity guidelines advisory committee concluded that there is now strong evidence that physical activity lowers the risk of seven types of cancer (namely colon, breast, kidney, endometrium, bladder, and stomach cancer, and oesophageal adenocarcinoma) although this evidence is derived from epidemiological studies.

Aerobic exercise is a form of physical activity and an accumulating body of evidence suggests that the incubation of cancer cells with post-exercise serum can have powerful effects on key hallmarks of cancer cell behaviour in vitro. I

n fact, a 2020 systematic review concluded that the transient serological responses to acute exercises reduce cancer cell growth, although many questions remain regarding the underlying mechanistic pathways and potential effect modifiers.

Nevertheless, while the evidence suggests a beneficial effect on cancer risk, in order to achieve a better understanding of how aerobic exercise affects the biological processes involved in cancer, requires comparison with a control group.

For the present study, the UK team recruited men with lifestyle risk factors for colon cancer e.g., older than 50 years of age, with a body mass index (BMI) > than 25 or a waist circumference > 94 cm and who did not engage in > 30 minutes of moderate physical activity at least 3 days/week over the previous 3 months.

The same participants served as their own control and undertook aerobic activity (6 x 5 minutes of cycling) and a control intervention (60 minutes of a quiet rested sitting), which was separated by a period of 2 to 7 days.

The team used LoVo cells, which served as a model of colon cancer and the primary outcome of the study was the mean difference in LoVo cell proliferation between exercise and control conditions. A total of 7 cytokines were quantified including interleukins (IL-) 6, 8 and 10 as well as markers of DNA damage such as γ-H2AX, were assessed.

Aerobic exercise and LoVo cell response

A total of 16 men with a mean age of 60 years and mean BMI of 29.9 were included in the study.

After stimulation of the LoVo cells with post-exercise serum, there was a decrease in cell proliferation compared to pre-exercise serum (-4.2%, 95% CI -6.8 to -1.5%, p = 0.006). In contrast, during the control period, there was a post-control increase in cell proliferation compared to pre-control serum (5.4%, 95% CI 2.2 to 8.6%, p = 0.003).

After adjustment for pre-values, the authors calculated that exercise-conditioned serum reduced cell proliferation compared to control by 5.7% (95% CI -8.8 to -2.6%, p = 0.002).

Turning to changes in biological markers, the researchers found that exercise reduced levels of γ-H2AX by 24% (p = 0.029) which reflected a decrease in DNA damage. In addition, the acute bout of aerobic exercise only significantly increased expression of one marker, IL-6, by 24.6% (p = 0.002).

The authors concluded the increased IL-6 expression may help explain the observed benefits of aerobic exercise in epidemiological studies and could account for why exercise helps to reduce colon cancer risk.

Citation
Orange ST et al. Acute aerobic exercise‐conditioned serum reduces colon cancer cell proliferation in vitro through interleukin‐6‐induced regulation of DNA damage Int J Cancer 2022