Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that include various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms in GSTM1 (a member of GST) and CYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in the GSTM1 and CYP1A1 genes and their relation to lung cancer susceptibility.
Malignant neoplasm of lung ; seconds ; CYP1A1 gene ; GST Gene ; Cytochrome P-450 CYP1A1

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that in clude various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms inGSTM1 (a member of GST) andCYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in theGSTM1 andCYP1A1 genes and their relation to lung cancer susceptibility.

The number of fatalities in Japan attributable to lung cancer exceeded 50000 in 2001. It is socially desirable that various markers, which can be utilized for the prevention of lung cancer, be established. We believe that smoking or exposure to carcinogens in air induces mutations in bronchial and alveolar epithelia, leading to the development of lung cancer. It would be useful to have markers of individual differences in susceptibility to chemical carcinogen-induced lung cancer 1) to identify genetic polymorphisms of enzymes metabolizing chemical carcinogens and 2) to investigate the expression of enzymes metabolizing chemical carcinogens. In this paper, we review CYP expression in the bronchial epithelium. CYP1, CYP2 and CYP3 are expressed in the bronchial epithelium. We also show the relationship between the genetic polymorphisms of cytochrome P450 (CYP) and a person's susceptibility to chemical carcinogen-induced lung cancer. We demonstrate the relationship between cigarette consumption and the CYP expression profile in the bronchial epithelium. To maintain and promote public health, we must apply evidence, such as CYP polymorphisms and CYP profiles to disease prevention and also to aggressively advance evidence-based prevention (EBP) of lung cancer.

In this study, we aim to compare the criteria for sensitizers among national organizations in various countries and international organizations, and to specify whether each Pollutant Release and Transfer Register (PRTR)-designated chemical substance is a sensitizer by each organization. The definition of sensitizing chemicals and the designation of respective sensitizers according to the PRTR law, Japan Society for Occupational Health (JSOH), American Conference of Governmental Industrial Hygienists (ACGIH), European Union (EU), and Deutsche Forschungsgemeinshaft (DFG) were studied. Of the 435 PRTR-designated chemical substances, 15 are listed as sensitizers according to the PRTR law, 16 as sensitizers of the airway and 21 as sensitizers of the skin by JSOH, 12 as sensitizers (no discrimination) by ACGIH, 19 (airway) and 85 (skin) by EU, and 15 (airway) and 43 (skin) by DFG. Only 9 substances were designated as sensitizers by all these organizations. The variation in the designation of sensitizers is accounted for by the differences in the classification criteria and grouping of chemical substances. JSOH limits the definition of sensitizers to substances that induce allergic reactions in humans and uses only human data. Other organizations utilize not only human evidence but also appropriate animal tests. In addition, EU designates an isocyanate as a sensitizer except those for which there is evidence showing that they do not cause respiratory sensitivity. The worldwide enforcement of the globally harmonized system (GHS) of classification and labeling of chemicals could promote not only the consistent designation of sensitizers among national and international organizations, but also the development of testing guidelines and classification criteria for mixtures.