| Project/Area Number |
09670361
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KIYOHARA Chikako Kyushu Univ., Graduate School of Med. Sci. Assistant Professor, 医学系研究科, 講師 (00169963)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Yoichi Kyushu Univ., Graduate School of Med. Sci. Associate Professor, 大学院・医学系研究科, 助教授 (20172356)
TANAKA Keitaro Kyushu Univ., Graduate School of Med. Sci. Research Assistant, 大学院・医学系研究科, 助手 (50217022)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Lung cancer / Aryl hydrocarbon hydroxylase / Cytochrome P4501A1 / Glutathione S-transferase M1 / CYPIAI遺伝子多型 / GSTMI遺伝子多型 / CYP1A1遺伝子多型 / GSTM1遺伝子多型 |
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| Research Abstract |
Cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs) are considered to be responsible for the activation or inactivation of benzo(a)pyrene (BP) and other polycyclic aromatic hydrocarbons in cigarette smoke to carcinogens. We investigated polymorphisms of CYP1A1 (Msp I and Ile-Val) and GSTs (M1 and T1) in 189 lung cancer patients. We also measured phenotypic activity of CYP1A1(aryl hydrocarbon hydroxylase, AHH) in peripheral mitogen-treated lymphocytes.
No relationship was observed between age-, cigarette dose- and season of the year-adjusted AHH activity and histologic type of tumor or TNM stage. Adjusted AHH inducibility of genotype C (geometric mean and 95% confidence interval (CI) ; 17.8 and 114.0-22.7) in Msp I polymorphism was significantly higher than those of the other two genotypes (P<0.0001), while no significant difference was observed between genotypes A (5.0 and 6.0) and B (5.5 and 4.7-6.4). On the other hand, non-induced AHH activity of genotype Val/Val (0.141 and 0.105-0.190pmol/min/10ィイD16ィエD1 cells) in isoleucinevaline (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.035 and 0.030-0.41 pmol/min/10ィイD16ィエD1 cells) and Ile/Val (0.034 and 0.027-0.43 pmol/min/10ィイD16ィエD1 cells) (P<0.0001). Irrespective of histologic type, TNM stage, CYP1A1 genotype or GSTM1 genotype, aromatic-DNA adduct levels were not distinguishable.
Variant genotype at the Msp I site associated with high AHH inducibility, while variant genotype in Ile-Val polymorphism was significantly related to increased the level of CYP1A1 catalytic activity. This association among lung cancer patients was more exaggerated than healthy controls reported previously.
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