Glutathione S-transferases and aromatic DNA adducts in smokers’ bronchoalveolar macrophages

Piipari, Ritva; Nurminen, Tuula; Savela, Kirsti; Hirvonen, Ari; Mäntylä, Timo; Anttila, Sisko

doi:10.1016/s0169-5002(02)00510-x

Cited by 26 publications

(10 citation statements)

References 22 publications

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“…In vitro assays further underline the complexity of the functional impact of the GSTP1 Ile105Val polymorphism, since the relative activity of the variants is substrate dependent [59]. GSTP1 , the most abundantly expressed member of the GST gene family in the lung [60], may have a complex impact on respiratory disease. GSTP1 appears to act not only as a detoxifying and antioxidative enzyme, but also as direct inhibitor of the C-Jun N terminal kinase [61].…”

Section: Discussionmentioning

confidence: 99%

Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

et al. 2007

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Background: Understanding the environmental and genetic risk factors of accelerated lung function decline in the general population is a first step in a prevention strategy against the worldwide increasing respiratory pathology of chronic obstructive pulmonary disease (COPD). Deficiency in antioxidative and detoxifying Glutathione S-transferase (GST) gene has been associated with poorer lung function in children, smokers and patients with respiratory diseases. In the present study, we assessed whether low activity variants in GST genes are also associated with accelerated lung function decline in the general adult population.

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Section: Discussionmentioning

confidence: 99%

Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

et al. 2007

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“…GSTP and M3 are specifically expressed in the lung, in bronchial and bronchiolar epithelium and in alveolar macrophages (Piipari et al 2003). However, the tissuespecific expression of GST has not been extensively investigated (Hayes and Strange 2000).…”

Section: Introductionmentioning

confidence: 99%

Expression patterns and novel splicing variants of glutathione-S-transferase isoenzymes of human lung and hepatocyte cell lines

et al. 2006

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Polymorphic glutathione S-transferase (GST) enzymes are involved in the metabolism of xenobiotics. They are of particular interest when studying disease susceptibility and adverse drug responses. The present work deals with the genetic polymorphisms and expression of the five GST classes (alpha, mu, pi, theta and zeta) in human lung and hepatocyte cell lines. We have determined their bioavailability for in vitro approaches. Common genetic polymorphisms of GSTM1 (*0, null), GSTT1 (*0) and GSTP1 (*A/*B, I105V) are detectable. The frequencies of the polymorphisms are within the expected range for a Caucasian population with one exception. The GSTM1*0 allele is 1.5-fold more frequent in lung cell lines. GST mRNAs are frequently but not uniformly distributed among unstimulated in vitro conditions. Lung cell lines show an approximately six-fold higher total GST transcript expression than hepatocyte cell lines. Additional GST transcripts have been identified for GSTT1; they represent alternative new splicing variants that occur in cancerous cell lines and in healthy lung tissue and blood. GST enzyme activity is mainly influenced by GSTP1. The activity promoted by 1-chloro-2,4-dinitrobenzene is significantly correlated to the GSTP1 mRNA expression level (R2=0.77, P<0.001). Individual human cell lines thus express GST isoenzymes in a similar pattern to human tissue. The most common genetic polymorphisms are present among the cell lines and have to be considered for in vitro stimulation approaches in a combinatory pattern.

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“…Some of the GST enzymes have also been found to be expressed in lung tissue. 56,57 However, GST expression in human tissue has not been extensively investigated. 58 GSTM1, GSTP1, and GSTT1 have been the most commonly investigated genes of the GST superfamily.…”

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confidence: 99%

Epidemiology of carcinogen metabolism genes and risk of squamous cell carcinoma of the head and neck

Wei

2007

Head & Neck

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The risk association between tobacco and alcohol use with squamous cell carcinoma of the head and neck (SCCHN) is well recognized. However, clearly not all individuals who smoke or drink develop SCCHN. Individual genetic susceptibility differences in carcinogen-metabolizing enzyme function, mutagen sensitivity, apoptosis, and chromosomal aberrations either alone or in combination have been theorized to modify the risk of SCCHN. Nearly all carcinogens and procarcinogens require activation by metabolizing enzymes. Similarly, detoxifying enzymes exist and deactivate carcinogens as well as their intermediate by-products. Together these enzymes are termed xenobiotic-metabolizing enzymes; genetic polymorphisms of these enzymes can modify an individual's response to carcinogens and hence the carcinogenic potential of such exposures. In this review, we explore the available evidence in recent literature regarding the risk association between SCCHN and various xenobiotic-metabolizing enzymes, including cytochrome P450s, glutathione S-transferases, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, alcohol dehydrogenase, and aldehyde dehydrogenase.

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Glutathione S-transferases and aromatic DNA adducts in smokers’ bronchoalveolar macrophages

Cited by 26 publications

References 22 publications

Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

Expression patterns and novel splicing variants of glutathione-S-transferase isoenzymes of human lung and hepatocyte cell lines

Epidemiology of carcinogen metabolism genes and risk of squamous cell carcinoma of the head and neck

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