RESUMEN
Vinyl chloride monomer (VCM) is a confirmed carcinogen. The effects of VCM on telomeres and the gene expression of telomere complex proteins, shelterin, have not been well studied but could be of potential relevance to the carcinogenic mechanism of VCM and the health surveillance of VCM-exposed workers. A group of 241 VCM-exposed workers and 101 internal controls from the same plant in Shandong, China were recruited and quantitative polymerase chain reaction was preformed to measure relative telomere length (RTL) and gene expression of shelterin proteins. VCM cumulative exposure dose (CED) was estimated for the exposed workers. The differences in RTL and gene expression between groups were compared by Wald test fitted with robust regression. Shorter RTL was observed in VCM-exposed workers than in the controls (P < 0.001) and was related to CED of VCM. Shortened RTL was also significantly related to increasing age (P = 0.012) and high blood pressure (P = 0.056). Levels of gene expression of shelterin components in exposed workers were all lower than in controls except increased TIN2 expression, and the gene expression differences in TIN2 and POT1 among exposed and control groups were significant (P = 0.014 for TIN2 and P < 0.001 for POT1, respectively). VCM exposure is found associated with altered telomere length and gene expression of shelterin components. This provides new insights into the potential carcinogenic mechanisms of VCM and could be helpful for the health surveillance for VCM-exposed workers. Environ. Mol. Mutagen. 60:361-367, 2019. © 2018 Wiley Periodicals, Inc.
Asunto(s)
Carcinógenos/toxicidad , Exposición Profesional/efectos adversos , Homeostasis del Telómero/efectos de los fármacos , Proteínas de Unión a Telómeros/genética , Cloruro de Vinilo/toxicidad , Adulto , China , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Complejo Shelterina , Acortamiento del Telómero/efectos de los fármacosRESUMEN
Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P50 value, with other 50 lead-unexposed workers as a control group. The cytokinesis-blocked micronucleus (CBMN) assay was performed to detect chromosomal damage of PBLs of both lead-exposed and -unexposed workers. The methylation-specific polymerase chain reaction (MSP-PCR) was further used to examine the methylation status of six TSGs (GSTP1, hMLH1, MGMT, p14, p15, and p16). Results showed that MN frequencies of high B-Pb workers 8.1 ± 3.1 and low B-Pb workers 5.7 ± 2.3 were significantly higher than that of control group 2.8 ± 1.9 (P < 0.01), while the MN frequency of high B-Pb workers was also higher than that of the low B-Pb workers (P < 0.01). The MN frequency in PBLs of lead-exposed group with the methylated TSGs was significantly higher than that in PBLs with the unmethylated TSGs (P < 0.05). Notably, the CpG island methylator phenotype (CIMP) correlated with chromosome damage (P < 0.05). Additionally, workers with high B-Pb had higher chromosome damage than those with low B-Pb (P < 0.05). Taken altogether, the results suggest that lead-exposed workers with CIMP positive and high B-Pb have a higher risk of being vulnerable to tumorigenesis. Environ. Mol. Mutagen. 59:549-556, 2018. © 2018 Wiley Periodicals, Inc.
