High benzo[a]pyrene diol-epoxide DNA adduct levels in lung and blood cells from individuals with combined CYP1A1 MspI/MspI-GSTM1*0/*0 genotypes

Rojas, Margarita; Alexandrov, K.; Cascorbi, Ingolf; Brockm??ller, J.; Likhachev, A.; Pozharisski, K.; Bouvier, G.; Auburtin, G.; Mayer, L.; Kopp-Schneider, A.; Roots, Ivar; Bartsch, Helmut

doi:10.1097/00008571-199804000-00003

Cited by 123 publications

(57 citation statements)

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“…mRNA expression studies showed relative expression of CYP2D6 in myeloblastic and lymphoid cell lines [5]. CYP1A1*2A variant has an increased activity, associated with a higher level of DNA adduct formation, and increased risk of carcinogenesis [48][49][50][51]. CYP1 family enzyme expressions are increased in myeloblastic and lymphoid cell lines, and CYP1 enzymes may contribute to the carcinogenesis of hematopoietic cells [5].…”

Section: Discussionmentioning

confidence: 99%

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

Sayitoğlu¹,

Hatırnaz²,

Erensoy³

et al. 2006

Am. J. Hematol.

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Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI ¼ 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1''null'' variants and the risk of acute leukemia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 ''null'' variants to the development of acute leukemias. Am.

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Section: Discussionmentioning

confidence: 99%

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

Sayitoğlu¹,

Hatırnaz²,

Erensoy³

et al. 2006

Am. J. Hematol.

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“…The first three methods can in principle be used for both identification of specific adducts and quantification, but they often lack the required sensitivity for practical use in molecular epidemiologic studies. However, fluorescence spectroscopy has been successively employed for the detection of DNA adducts derived from B[a]P in individuals exposed to PAHs (Rojas et al 1994(Rojas et al , 1998. In human monitoring, peripheral blood cells such as leukocytes and lymphocytes are most frequently used as the source of DNA, but biopsies from target tissues have also been studied.…”

Section: Pah Exposure In Humansmentioning

confidence: 99%

“…The adducts identified after PAH exposure have been classified as aromatic or lipophilic, and only in a very few cases have the adducts been identified (Phillips 1996;Rojas et al 1998).…”

Section: Pah Exposure In Humansmentioning

confidence: 99%

“…A growing number of studies link the mutations in the CYP1A1 gene to increased susceptibility to DNA damage. The allele carrying the Ile to Val mutation was more commonly found in lung parenchyma DNA from lung cancer patients and in white blood cells from PAH-exposed individuals with high levels of DNA adducts derived from anti-BPDE (Rojas et al 1998(Rojas et al , 2000. This allele was also associated with increased occurrence of p53 mutations in tumor tissue (Kawajiri et al 1996;Lazarus et al 1998;Przygodzki et al 1998).…”

Section: Pah Exposure In Humansmentioning

confidence: 99%

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Cancer Risk Assessment, Indicators, and Guidelines for Polycyclic Aromatic Hydrocarbons in the Ambient Air

Boström¹,

Gerde²,

Hanberg³

et al. 2002

Environ Health Perspect

852

454

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“…Several investigations have suggested an increased sensitivity of the GSTM1 null genotype to genotoxicity induced by various exposures, including tobacco smoke (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). Such an association was not, however, unequivocally demonstrated in most of the few studies where SCEs or MN were used as biomarkers (48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58).…”

Section: Discussionmentioning

confidence: 99%

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

Pitarque

Vaglenov

Nosko

et al. 2002

Environ Health Perspect

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We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.

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High benzo[a]pyrene diol-epoxide DNA adduct levels in lung and blood cells from individuals with combined CYP1A1 MspI/MspI-GSTM10/0 genotypes

Cited by 123 publications

References 0 publications

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

Cancer Risk Assessment, Indicators, and Guidelines for Polycyclic Aromatic Hydrocarbons in the Ambient Air

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

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