Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers

Abstract

<jats:p> To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py’s level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py’s level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs’ p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers. </jats:p>

Aberrant DNA Methylation of Two Tumor Suppressor Genes, p14ARF and p15INK4b , after Chronic Occupational Exposure to Low Level of Benzene

“…Higher rates of p14 ARF and p15 INK4b methylation are reported in coke oven workers exposed to airborne benzo[a]pyrene (10.7% and 22.3%, respectively) where the frequency of p14 ARF hypermethylation depends on work experience; that of p15 INK4b does not. 21 Our findings did not reveal any associations between the frequency of promoter methylation of p14 ARF and p15 INK4b and either of age, smoking habit, and work experience. That would be attributed to the low sample size of our study.…”

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

“…Promoter methylation of the tumor suppressor genes p14 ARK and p16 INK4 was increased in peripheral blood mononuclear cells, along with increased urinary levels of 1-hydroxypyrene (an indicator of exposure to PAHs) in coke oven workers relative to water pump workers [147]. DNA damage, as evaluated by a comet assay, was also significantly higher in the coke oven workers.…”

Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents

“…In 2015, Zhang et al ( 38 ) examined methylation of the p14 ( ARK ), p15 ( INK4b ), and p16 ( INK4a ) genes in coke oven workers. The three genes studied were hypermethylated, with two of these correlated with years worked and also with urinary 1-OHP levels.…”