RESUMEN
Hexavalent chromium [Cr(VI)] is one of the most common environmental carcinogens, which is associated with DNA damage, genetic instability and increase the risk of cancer development. However, the mechanisms of genetic damage induced by Cr(VI) remains to be thoroughly illustrated. A molecular epidemiological study was conducted on 120 chromate exposed workers and 97 controls. Results indicated that,the rs12432907 of XRCC3 carrying T allele, the rs144848 of BRCA2 with C allele and the rs1805800 of NBS1 with genotype(TT) of individuals were associated with lower genetic damage, while the rs2295152 of XRCC3 carrying T allele, the rs13312986 (CC and CT genotypes) and the rs2697679 of NBS1 with A allele were associated with higher genetic damage in workers exposed to chromate. The interaction of chromate exposure with rs2295152 of XRCC3 had a significant effect on micronuclei frequency (MNF). The gene polymorphisms in homologous recombination repair pathway could modulate chromate-induced genetic damage.
Asunto(s)
Carcinógenos Ambientales/toxicidad , Cromo/toxicidad , Proteínas de Unión al ADN/genética , Exposición Profesional/efectos adversos , Adulto , Daño del ADN , Femenino , Genotipo , Humanos , Linfocitos/metabolismo , Masculino , Micronúcleos con Defecto Cromosómico , Polimorfismo Genético , Reparación del ADN por RecombinaciónRESUMEN
To examine the mechanism of hexavalent chromium [Cr(VI)]-induced carcinogenesis, a cross-sectional study in workers with or without exposure to Cr(VI) as well as in vitro administration of Cr(VI) in 16HBE cells was conducted. We explored the associations between Cr(VI) exposure, methylation modification of DNA repair genes and their expression levels, and genetic damage. Results showed that hypermethylation of CpG sites were observed in both occupationally exposed workers and 16HBE cells administrated Cr(VI). DNA damage markers including 8-hydroxydeoxyguanosine (8-OHdG) and micronucleus frequency in Cr(VI)-exposed workers were significantly higher than the control group. Among workers, blood Cr concentration was positively correlaed with the methylation level of CpG sites in DNA repair genes including CpG6,7, CpG8, CpG9,10,11 of MGMT, CpG11 of HOGG1; CpG15,16,17, CpG19 of RAD51, and genetic damage markers including 8-OHdG and micronucleus frequency. Significant negative association between methylation levels of CpG sites in DNA repair genes and corresponding mRNA was also observed in 16HBE cells. This indicated that Cr(VI) exposure can down-regulate DNA repair gene expression by hypermethylation, which leads to enhanced genetic damage. The methylation level of these CpG sites of DNA repair genes can be potential epigenetic markers for Cr(VI)-induced DNA damage.
Asunto(s)
Cromo/metabolismo , Reparación del ADN/efectos de los fármacos , Contaminantes Ambientales/metabolismo , Exposición Profesional/análisis , 8-Hidroxi-2'-Desoxicoguanosina , Biomarcadores , Recuento de Células , Línea Celular , Cromo/toxicidad , Estudios Transversales , Daño del ADN , Metilación de ADN , Desoxiguanosina/análogos & derivados , Regulación hacia Abajo/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Humanos , Exposición Profesional/estadística & datos numéricos , ARN MensajeroRESUMEN
Cr(VI) is widely-recognized as occupational and environmental contaminant, but the precise underlying mechanisms of Cr(VI) induced carcinogenic toxicity remain to be elucidated. Among kinds of toxic mechanisms, alteration of protein profiling usually elaborate a key mechanism of Cr(VI) induced toxicity and carcinogenesis. Large-scale proteins changes can reflect the onset or progression of carcinogenic toxicity, and potential serum protein biomarkers of Cr(VI) exposure. To gain an insight into the serum proteins expression profiling in chromate workers and find potential novel serum proteins biomarkers of Cr(VI) exposure, 107 male participants from a chromate production plant were recruited into the study. Questionnaire was applied to collect personal information and occupational history. Chromium concentration in blood (CrB) was measured to evaluate the participants' internal exposure. Serum proteins profiling and bioinformatics analysis were performed to explore differentially expressed proteins, proteins-chemical interaction network, critical proteins nodes related to the signaling pathways among 16 controls and 25 exposure workers in the first stage. ELISA tests were applied to verify the critical interested proteins nodes in the remaining 41 exposure workers and 25 controls. The results showed that the CrB levels in the control group were significantly lower than that in the exposure group (P<0.05). 44 significantly differentially expressed serum proteins formed 16 significant signaling pathways and a complex proteins-chemical interaction network, which associated with the immune system and extracellular matrix organization. C reactive protein (CRP), sonic hedgehog protein (SHH) and calcium located at critical nodes in proteins-chemical interaction network. There was a significant negative correlation between serum CRP level and CrB (P<0.05), and a significant positive correlation between SHH concentrations and CrB (P<0.05), which indicated that CRP and SHH might be as the potential novel biomarkers of Cr(VI) exposure. Also, the current study preliminarily paved the way to further functional studies to understand the underlying mechanisms and novel serum biomarkers of Cr(VI) exposure.
Asunto(s)
Proteínas Sanguíneas/análisis , Cromo/efectos adversos , Biología Computacional , Instalaciones Industriales y de Fabricación , Exposición Profesional/efectos adversos , Salud Laboral , Proteómica/métodos , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Cromo/sangre , Monitoreo del Ambiente/métodos , Ensayo de Inmunoadsorción Enzimática , Proteínas Hedgehog/sangre , Humanos , Masculino , Mapas de Interacción de Proteínas , Medición de Riesgo , Transducción de Señal , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: The health surveillance proposal for chromate exposed workers was provided and analyzed on the evidence-based study and then to be improved. METHOD: Firstly, the related literatures were searched about liver damage, micronuclei, urinary chromium and hexavalent chromium exposure in Evidence Based Medicine Reviews such as Cochran library, OVID Medline, Web of knowledge in December 2011; and then, these literatures were reviewed in according to inclusion and exclusion criteria; 22 articles totally were retrieved, evaluated and classified in according to the grading standard by Oxford Centre for Evidence-based Medicine.Finally, field epidemiological investigation was further adopted to confirm the efficiency and feasibility of this proposal, combined with cost-effectiveness analysis:the ratio of total cost divided survival years was used to express the cost-effectiveness. RESULT: Only the glutamic pyruvic transaminase test could not reflect liver damage caused by chromate exposure well; Urinary chromium correlated well with the index reflecting body damage caused by chromate exposure; Binucleated cells micronucleus index in peripheral blood lymphocyte could reflect the genetic damage caused by chromate exposure. As for health economic evaluation of chromate lung cancer, the value of cost/effectiveness was ¥42 321.61 per year that was far below the value of common people (¥252 868.97 per year) . CONCLUSION: It was suggested that serum glutamic pyruvic transaminase test should be replaced by liver function test, urinary chromium should be classified as a compulsory index and binucleated cells micronucleus index in peripheral blood lymphocyte should be supplied as a recommended index.