An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans

none24noneS. BONASSI; A. ZNAOR; M. CEPPI; C. LANDO; W.P. CHANG; N. HOLLAND; M. KIRSCH-VOLDERS; E. ZEIGER; S. BAN; R. BARALE; M.P. BIGATTI; C. BOLOGNESI; A. CEBULSKA-WASILEWSKA; E. FABIANOVA; A. FUCIC; L. HAGMAR; G. JOKSIC; A. MARTELLI; L. MIGLIORE; E. MIRKOVA; M.R. SCARFI; A. ZIJNO; H. NORPPA; M. FENECHS., Bonassi; A., Znaor; M., Ceppi; C., Lando; W. P., Chang; N., Holland; M., KIRSCH VOLDERS; E., Zeiger; S., Ban; R., Barale; M. P., Bigatti; C., Bolognesi; A., CEBULSKA WASILEWSKA; E., Fabianova; A., Fucic; L., Hagmar; G., Joksic; Martelli, ANTONIETTA MARIA; L., Migliore; E., Mirkova; M. R., Scarfi; A., Zijno; H., Norppa; M., Fenec

Novel epigenetic changes unveiled by monozygotic twins discordant for smoking habits.

Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population

HUman MicroNucleus Project: International Database

stituto Nazionale per la Ricerca sul Molecular Toxicology Laboratory, Third Military Medical University, Chong Qing, China Laboratorio Dosimetria Biologica, Autoridad Regulatoria Nuclear, Buenos Aires, Argentina Auckland Cancer Society Research Centre, Auckland, New Zealand Institute for Medical Research end Occupational Health, Zagreb, Croatia Centro de Proteccion e Higiene de las Radiaciones, Havana, Cuba Department of Pharmacology, University of Bologna, Bologna, Italy Cell Biology Division, Bhabha Atomic Research Center, Mumbai, India Department of Radiation Oncology, Leo Jenkins Cancer Center, East Carolina University School of Medicine, Greenville, North Carolina Institute of Genetics and Cytology, Belarus Academy of Sciences, Minsk, Belarus Nacional Center of Hygiene, Medical Ecology and Nutrition, Sofia, Bulgaria Dipartimento di Agrobiologia e Agrochimica, Universita della Tuscia, Viterbo, Italy Institute fur Medizinische Strahlenbiologie,

Metabolic polymorphisms and urinary biomarkers in subjects with low benzene exposure

The effect of some common metabolic polymorphisms on the rate of trans,trans-muconic acid (TMA) and S-phenylmercapturic acid (SPMA) excretion was investigated in 169 policemen exposed to low benzene levels (g/m(3)) during the work shift. End-shift urinary concentrations of TMA and SPMA, normalized to unmetabolized blood benzene concentration, were used as indicators of individual metabolic capacity. CYP2E1, NQO1, GSTM1, and GSTT1 polymorphisms were analyzed in all subjects by polymerase chain reaction (PCR)-restriction fragment length (RFL). The results obtained show significantly elevated levels of TMA and SPMA in urine of smokers compared to nonsmokers, whereas no correlation with environmental benzene was observed. TMA/blood benzene ratio was partially modulated by glutathione S-transferase (GST) genotypes, with significantly higher values in null individuals (GSTM1 and GSTT1 combined). However, a greater fraction of total variance of TMA/blood benzene in the study population was explained by other independent variables, that is, season of sampling, smoking habits, and gender. Variance in SPMA/blood benzene ratio was only associated with smoking and occupation, whereas no significant role was observed for the metabolic polymorphisms considered. These results suggest that in a population exposed to very low benzene concentrations, urinary TMA and SPMA levels are affected to a limited extent by metabolic polymorphisms, whereas other factors, such as gender, lifestyle, or other confounders, may account for a larger fraction of the interindividual variability of these biomarkers