Occupational exposures to certain metals, hydrocarbons and ionizing radiation are associated with increased lung cancer in workers; because these exposures continue, lung cancer remains an important problem in industrialized nations. The gravity of the lung cancer, specifically the low cure rate associated with the disease, has forced researchers to focus efforts at developing biological indicators (biomarkers) of carcinogen exposure and early, reversible effects. This review examines critically the development of these biomarkers for occupational and environmenta exposures to polycyclic aromatic hydrocarbons (PAH), a ubiquitous class of lung carcinogens. Biomarkers of several different stages of the carcinogenic process have been proposed. Industrial hygiene and occupational health emphasize exposure and disease prevention. For this reason, biomarkers useful in industrial hygiene practice are those which measure events prior to the initiation phase of carcinogenesis; markers of later events which have a greater positive predictive value may measure irreversible effects and are more appropriate for disease screening and epidemiology. One of the strengths of biological monitoring is that exposures and effects can be measured regardless of route. Data indicates that the dermal route may be a significant pathway for delivery of PAH to the lung. This finding has important ramifications because as airborne exposure limits decrease the relative impact of dermal absorption is increased.
Carcinogens ; DNA Damage ; Gene Expression Regulation ; Genetic Markers ; Human ; Lung Neoplasms/chemically induced/*genetics ; Mutation ; Occupational Diseases/chemically induced/*genetics ; Oncogenes ; Polycyclic Hydrocarbons/adverse effects

OBJECTIVETo investigate the frequency of numerical aberrations for chromosomes 7 and 8 in the sperms of workers exposed to benzene series.

METHODSNumerical aberrations in the sperms of workers were detected by two-color fluorescence in situ hybridization with biotin labeled chromosome 7 probe (D7Z1) and digoxingenin labeled chromosome 8 probe (D8Z1).

RESULTSThe time-weight average air concentration (TWA) of benzene in the workshop was 42.29 mg/m(3), which was significantly higher than that of the national maximum allowable concentration [6 mg/m(3)]. The concentration of urinary trans,trans-muconic acid(ttMA) in the exposed group was also higher than that of the control group. In all, 155721 sperm nuclei from 15 workers in the exposed group and 123771 sperm nuclei from 12 individuals in the control group were examined. The results showed that the frequency of diploidy sperms and the frequencies of disomic sperm for chromosomes 7 and 8 in the exposed group (0.129%, 0.170%, 0.078%) were significantly higher than those of the control group (0.055%, 0.053%, 0.033%), respectively. The frequencies of nullisomic sperm for chromosomes 7 and 8 in the exposed group (0.165%, 0.088%) were also significantly increased, compared with those of the control group (0.056%, 0.029%). A statistically significant difference in the frequency of overall numerical chromosome aberrations was seen between the exposed group (0.745%) and the control group (0.289%).

CONCLUSIONThe results suggested that higher concentration of benzene may induce higher frequencies of numerical aberrations in the sperms of workers exposed to benzene series.

Adult ; Benzene ; poisoning ; Chromosome Aberrations ; chemically induced ; Chromosomes, Human, Pair 7 ; genetics ; Chromosomes, Human, Pair 8 ; drug effects ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Occupational Diseases ; diagnosis ; genetics ; Occupational Exposure ; analysis ; Spermatozoa ; drug effects ; metabolism

Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P < 0.05) and SNP analyses (FDR < 0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.
Adult ; Arachidonate 5-Lipoxygenase/genetics/*metabolism ; Benzene/toxicity ; Cell Count ; Cross-Sectional Studies ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Hematologic Diseases/chemically induced/genetics/*metabolism/pathology ; Humans ; Immunity, Innate/genetics ; Leukocytes/*drug effects/metabolism/pathology ; Male ; Occupational Exposure/adverse effects ; Peroxidase/genetics/*metabolism ; Polymorphism, Single Nucleotide ; Vascular Cell Adhesion Molecule-1/genetics/*metabolism

Exposure to cephalosporins could cause occupational allergic diseases in health care workers (HCWs). We evaluated the prevalence of serum specific IgE and IgG antibodies to cephalosporin-human serum albumin (HSA) conjugate and to identify potential genetic risk factors associated with sensitization to cephalosporins in exposed HCWs. The study population consisted of 153 HCWs who had been exposed to antibiotics in a single university hospital and 86 unexposed healthy controls. A questionnaire survey of work-related symptoms (WRS) was administered. A skin-prick test (SPT) was performed, and serum-specific IgE and IgG antibodies to 3 commonly prescribed cephalosporins were measured by ELISA. Four single-nucleotide polymorphisms of the candidate genes related to IgE sensitization were genotyped. The prevalence of WRS to cephalosporins was 2.6%. The prevalence rates of serum-specific IgE and IgG antibodies to cephalosporins were 20.3% and 14.7%, respectively. The FcepsilonR1beta-109T > C polymorphism was significantly associated with IgE sensitization to cephalosporins in HCWs (P = 0.036, OR = 3.553; CI, 1.324-9.532). The in vitro functional assay demonstrated that the T allele of FcepsilonR1beta-109T had greater promoter activity than did the C allele (P < 0.001). The FcepsilonR1beta-109T > C polymorphism may be a potential genetic risk factor for increased IgE sensitization to cephalosporins.
Adult ; Alleles ; Anti-Bacterial Agents/analysis/*immunology ; Cephalosporins/analysis/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Genetic Predisposition to Disease ; Health Personnel ; Humans ; Hypersensitivity/*diagnosis/epidemiology ; Immunoglobulin E/blood ; Immunoglobulin G/blood ; Male ; Occupational Diseases/*chemically induced/epidemiology ; Occupational Exposure ; Odds Ratio ; Questionnaires ; Receptors, IgE/genetics ; Skin Tests ; Young Adult