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Effects Of Genetic Polymorphism Of Metabolic Enzymes, Nutrition, And Lifestyle Factors On DNA Adduct Formation In Lymphocytes.

Y. Wang, M. Ichiba, M. Iyadomi, J. Zhang, K. Tomokuni
Published 1998 · Chemistry, Medicine

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Although cigarette smoking is one major determinant of lung carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens, nutrition, and lifestyle. Previous studies have shown that genetic polymorphism of metabolic enzymes and plasma micronutrients are associated with lung cancer risk. DNA adducts may serve as a molecular dosimeter for exposure to carcinogens. In this cross-sectional study, we analyzed the blood samples of 158 subjects to evaluate the effects of polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase M1 (GSTM1), T (GSTT), N-acetytransferase 2 (NAT2), and aldehyde dehydrogenase 2 (ALDH2) as well as the effects of plasma beta-carotene and alpha-tocopherol on lymphocyte DNA adducts measured by 32P-postlabeling analysis. The DNA adduct level of smokers (mean +/- SD, 1.26 +/- 0.79/10(8) nucleotides) was significantly higher than that of nonsmokers (0.87 +/- 0.33, P = 0.007). Smokers with CYP1A1 minor homozygotes and GSTM1 null genotypes had a significantly higher level of DNA adducts than those without (P = 0.027 for homozygotes, P = 0.049 for heterozygotes). Smokers with NAT2 minor homozygotes also tended to have a higher DNA adduct level than those with heterozygotes and wild alleles, but the difference was not statistically significant. The DNA adduct level of smokers with ALDH2 heterozygotes was significantly higher than that of smokers with minor homozygotes (P = 0.045). When smokers were divided into "high" and "low" groups according to mean level of plasma beta-carotene or alpha-tocopherol, in the low beta-carotene group, the subjects with CYP1A1 minor homozygotes had higher DNA adduct levels than those with other CYP1A1 genotypes. Smokers with GSTT null genotype and high beta-carotene tended to have a higher DNA adduct level than those with GSTT present and high beta-carotene (P = 0.07), and those with GSTT null genotype and low beta-carotene (P = 0.07). There was weak correlation between DNA adduct level and number of cigarettes smoked per day in the low plasma beta-carotene group (r = 0.28, n = 36, p < 0.1). These results suggested that polymorphisms of CYP1A1, GSTM1, T, NAT2, and ALDH2, and plasma beta-carotene may modulate the level of DNA adducts.
This paper references
Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population.
K. Nakachi (1993)
Can dietary / 3carotene materially reduce human cancer rates ?
R Peto (1981)
Effects of palm carotenoids in rat hepatic cytochrome P450-mediated benzo(a)pyrene metabolism.
B. Tan (1991)
Environmental air pollution and DNA adducts in Copenhagen bus drivers--effect of GSTM1 and NAT2 genotypes on adduct levels.
P. S. Nielsen (1996)
8-Hydroxydeoxyguanosine in human leukocyte DNA and daily health practice factors: effects of individual alcohol sensitivity.
M. Nakajima (1996)
Diverse carotenoids protect against chemically induced neoplastic transformation.
J. Bertram (1991)
Glutathione-S-transferase (GST) theta polymorphism influences backgroud SCE rate
KR Schroder (1995)
Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta.
H. Nelson (1995)
Nuclease P1-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts.
M. V. Reddy (1986)
Determination of cotinine by high performance liquid chromatography and evaluation of exposure to tabacco smoke
Y Yamano (1990)
Development of a 32P-postlabelling method for the analysis of adducts arising through the reaction of acetaldehyde with 2'-deoxyguanosine-3'-monophosphate and DNA.
J. L. Fang (1995)
Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility.
S. Zhong (1991)
Role of acetylation in colorectal cancer.
R. Minchin (1993)
An isocratic high-performance liquid chromatography method for the simultaneous analysis of plasma retinol, alpha-tocopherol, and various carotenoids.
K. Miller (1985)
Dietary /3-carotene and lung cancer risk in U.S
ST Mayne (1994)
Effects of β-carotene on chemically-induced skin tumors in HRASkh hairless mice
H. Steinel (1990)
High Susceptibility to Lung Cancer Analyzed in Terms of Combined Genotypes of P450IA1 and Mu‐class Glutathione S‐Transferase Genes
S. Hayashi (1992)
Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types.
A. K. Alexandrie (1994)
The effect of different levels of dietary beta-carotene on DMBA-induced salivary gland tumors.
B. Alam (1987)
Relationship between hprt mutant frequency, aromatic DNA adducts and genotypes for GSTM1 and NAT2 in bus maintenance workers.
S. Hou (1995)
Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males.
A. Yokoyama (1996)
beta-Carotene-mediated inhibition of a DNA adduct induced by 7,12-dimethylbenz(a)anthracene and 7-hydroxymethyl-12-methylbenz(a)anthracene in mouse mammary gland in vitro.
S. K. Das (1992)
Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk.
D. Ryberg (1997)
Low Km aldehyde dehydrogenase (ALDH2) polymorphism, alcohol-drinking behavior, and chromosome alterations in peripheral lymphocytes.
K. Morimoto (1996)
Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese
T. Oyama (1995)
Comparative antimutagenicity of 5 compounds against 5 mutagenic complex mixtures in Salmonella typhimurium strain TA98.
T. Ong (1989)
Can dietary beta-carotene materially reduce human cancer rates?
R. Peto (1981)
Simultaneous determination of plasma retinol, α-tocopherol, lycopene, α-carotene, and β-carotene by high-performance liquid chromatography
K. W. Miller (1984)
S. N. Wickramasinghe (1986)
Aromatic DNA adducts, micronuclei and genetic polymorphism for CYP1A1 and GST1 in chimney sweeps.
M. Ichiba (1994)
Isolation of DNA from blood.
T. L. Kendall (1991)
Contribution of genetic and nutritional factors to DNA damage in heavy smokers.
L. Mooney (1997)
Dietary beta carotene and lung cancer risk in U.S. nonsmokers.
S. Mayne (1994)
Relationship between plasma concentrations of beta-carotene and alpha-tocopherol and life-style factors and levels of DNA adducts in lymphocytes.
Y. Wang (1997)
Effect of alpha-tocopherol on the binding of benzo(a)pyrene to nuclear macromolecules.
T. Matsuura (1979)
Lymphocytes,DNA adducts and genetic polymorphism for metabolic enzymes in low dose cigarette smokers.
M. Ichiba (1998)
Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population.
W. Blot (1993)
Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism.
S. Pemble (1994)
Role of genetics and drug metabolism in human cancer risk.
D. Nebert (1991)
Effects of beta-carotene on chemically-induced skin tumors in HRA/Skh hairless mice.
H. Steinel (1990)
Antitumor activity in skin of Skh and Sencar mice by two dietary beta-carotene formulations.
L. Lambert (1990)
Lung cancer, race, and a CYP1A1 genetic polymorphism.
P. Shields (1993)
Inhalation toxicity of acetaldehyde in rats. III. Carcinogenicity study.
R. Woutersen (1986)
Point-mutational MspI and Ile-Val polymorphisms closely linked in the CYP1A1 gene: lack of association with susceptibility to lung cancer in a Finnish study population.
A. Hirvonen (1992)
Environmental air pollution and DNA adducts in Copenhagen bus driversof GSTMI and NAT 2 genotypes on adduct levels
PS Nielsen (1996)
Does beta-carotene explain why reduced cancer risk is associated with vegetable and fruit intake?
R. Ziegler (1992)
Genotypes of glutathione transferase M 1 and P 1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis 18,1285-9
D Ryberg (1997)
Polycyclic aromatic hydrocarbon-DNA adducts in smokers and their relationship to micronutrient levels and the glutathione-S-transferase M1 genotype.
R. Grinberg-Funes (1994)
Elevated levels of hemoglobin-associated acetaldehyde related to alcohol drinking in the atypical genotype of low Km aldehyde dehydrogenase.
T. Takeshita (1997)
Genetically based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens
P. Vineis (1994)

This paper is referenced by
Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk
W. Au (2001)
Pooled analysis of studies on DNA adducts and dietary vitamins.
C. Ragin (2010)
Detection of Methylation Damage in DNA of Gastric Cancer Tissues Using 32P‐Postlabelling Assay
D. Kim (1999)
DNA adduct burden and tobacco carcinogenesis
J. Wiencke (2002)
Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes
J. Zhang (2000)
Lymphocyte DNA Damage and Anti-Oxidative Parameters are Affected by the Glutathione S-Transferase (GST) M1 and T1 Polymorphism and Smoking Status in Korean Young Adults
Jeong-Hwa Han (2011)
Glutathione-S-Transferase polymorphisms as risk factors for lung cancer : A case-control study
C. E. Caplan (2004)
Maternal occupational chemical exposures and biotransformation genotypes as risk factors for selected congenital anomalies.
G. Shaw (2003)
Analysis of 13 (32)P-DNA postlabeling studies on occupational cohorts exposed to air pollution.
M. Peluso (2001)
Polymorphism of Glutathione S-Transferases M1 and T1 in Several Populations of Russia
S. Popova (2004)
Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study.
Q. Wei (2000)
Risk of limb deficiency defects associated with NAT1, NAT2, GSTT1, GSTM1, and NOS3 genetic variants, maternal smoking, and vitamin supplement intake
S. Carmichael (2006)
[Risk assessment of environmental carcinogenesis using WBC DNA adducts].
M. Ichiba (2004)
Carotenoids and Vitamin A in Lung Cancer Prevention
A. Iskandar (2013)
Smoking and Lung Disease
K. Haustein (2010)
Metabolic and DNA Repair Variations in Susceptibility to Genotoxins
S. Pavanello (2003)
Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations.
P. Georgiadis (2005)
Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population‐based prognostic study
A. Andrew (2015)
Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers.
L. Mooney (2005)
Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults.
D. Palli (2003)
Impact of phase I or phase II enzyme polymorphisms on lymphocyte DNA adducts in subjects exposed to urban air pollution and environmental tobacco smoke.
P. Georgiadis (2004)
Urinary 1-hydroxypyrene in coke oven workers relative to exposure, alcohol consumption, and metabolic enzymes
J. Zhang (2001)
Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility.
E. Reszka (2006)
Ethique en médecine du travail, aptitude médicale au travail et tests génétiques : réflexions sur l'introduction des tests prédictifs en médecine du travail
F. Rosenfeld (2000)
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