Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers

Kim, James H.; Sherman, Mark E.; Curriero, Frank C.; Guengerich, F. Peter; Strickland, Paul T.; Sutter, Thomas R.

doi:10.1016/j.taap.2003.11.015

Cited by 139 publications

(74 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significantly increased expression levels of CYP1B1 as compared with CYP1A1 in nontumor and tumor human lung tissues has been reported (5,6). In contrast, a recent study indicated that the CYP1B1 protein is expressed at levels 1/10 of those of CYP1A1 in lungs of nonsmokers and smokers (7). Some studies have indicated that CYP1B1 is more active than CYP1A1 in B[a]P activation (8,9) whereas others have implicated that CYP1A1 is more active (2).…”

Section: [A]p-78-dihydroepoxide Which Is Further Hydrolyzed By Micrmentioning

confidence: 95%

“…Some studies have indicated that CYP1B1 is more active than CYP1A1 in B[a]P activation (8,9) whereas others have implicated that CYP1A1 is more active (2). However, enzyme induction caused by smoking results in 10-fold higher levels of both CYP1A1 and CYP1B1 proteins and about 10% of the population shows much greater enzyme induction (7,10). Because CYP1A1 and CYP1B1 are known to bioactivate procarcinogens found in cigarette smoke, both enzymes might play important role in lung carcinogenesis.…”

Section: [A]p-78-dihydroepoxide Which Is Further Hydrolyzed By Micrmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Common CYP1B1 Variants with Different Capacity for Benzo[a]pyrene-7,8-Dihydrodiol Epoxide Formation from Benzo[a]pyrene

et al. 2005

View full text Add to dashboard Cite

Cytochrome P450 1B1 (CYP1B1), an extrahepatic enzyme inducible by smoking, is overexpressed in many tumors and catalyzes the metabolic activation of procarcinogens such as polycyclic aromatic hydrocarbons. In human, CYP1B1 is genetically polymorphic and five common missense mutations causing amino acid substitution have been identified. In this study, we have investigated CYP1B1 haplotypes present in a Spanish population and carried out functional analyses of the corresponding enzymes in yeast using benzo [a]pyrene as a substrate. CYP1B1*1, CYP1B1*2, CYP1B1*3, CYP1B1*4, CYP1B1*6, and CYP1B1*7, encoding combinations of the Arg48Gly, Ala119Ser, Leu432Val, Asn453Ser, and Ala443Gly amino acid substitutions, were present at frequencies of 14.3%, 25.5%, 38.8%, 18.1%, 0.4%, and 2.6%, respectively. The variant CYP1B1 forms were heterologously expressed with human reductase in Saccharomyces cerevisiae and kinetic analyses of benzo[a]pyrene metabolism were carried out. CYP1B1.7, having the amino acid substitutions Arg48Gly, Ala119Ser, Leu432Val, and Ala443Gly, exhibited a significantly decreased capacity (P < 0.001) for the formation of (F)-benzo[a]pyrene-trans-7,8-dihydrodiol from benzo[a]-pyrene as indicated by lower intrinsic clearance (V max / K m ). A somewhat decreased clearance was observed for CYP1B1.4, whereas no significant differences in kinetic properties among the remaining variant enzymes were observed as compared with CYP1B1.1. Thus, genetic polymorphism in the CYP1B1 gene, as defined by the haplotypes investigated, might cause interindividual differences in susceptibility (e.g., to lung cancer induced by smoking). The results indicate the necessity to make molecular epidemiologic investigations regarding the association of the specific CYP1B1 haplotypes and cancer risk. (Cancer Res 2005; 65(12): 5105-11)

show abstract

Section: [A]p-78-dihydroepoxide Which Is Further Hydrolyzed By Micrmentioning

confidence: 95%

Section: [A]p-78-dihydroepoxide Which Is Further Hydrolyzed By Micrmentioning

confidence: 99%

Characterization of Common CYP1B1 Variants with Different Capacity for Benzo[a]pyrene-7,8-Dihydrodiol Epoxide Formation from Benzo[a]pyrene

et al. 2005

View full text Add to dashboard Cite

show abstract

“…It should be noted that these findings were based on 109 cases and 423 controls, of which only 9 individuals carried the C/C genotype. While an early functional study suggested that CYP1A1 MspI variant genotypes result in increased ethoxyresorufin-O-deethylase (EROD) activity [21], later studies suggest that differing expression levels are due to polymorphisms in CYP1A1 exon 7 Ile 462 Val [22,23], and may also be influenced by smoking status [24] and gender [25,26].…”

Section: Cyp1a1 Mspimentioning

confidence: 99%

Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: A population-based study

et al. 2007

View full text Add to dashboard Cite

Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a populationbased case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sexmatched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 exon 7 Ile 462 Val and CYP1B1 Leu 432 Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 MspI or CYP1B1 Leu 432 Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the Ile/Val genotype at CYP1A1 exon 7 locus were at decreased risk of having lung cancer compared to those with the Ile/Ile genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR=0.41 95% CI 0.19-0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.

show abstract

“…6, 7 This idea is supported by studies using human patients in which a number of AHR target genes, such as CYP1A1 and CYP1B1 have been found to be upregulated in the epithelial cells of the respiratory tract of smokers as compared to that of nonsmokers. 8,9 Senescence is an irreversible growth arrest state maintained even in the presence of mitogenic stimuli. 10, 11 A senescent phenotype can be induced in normal cells by many distinct signals.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke condensate and dioxin suppress culture shock induced senescence in normal human oral keratinocytes

Zhang

Dingle

et al. 2007

Oral Oncology

View full text Add to dashboard Cite

The aryl hydrocarbon receptor is a ligand activated transcription factor which regulates biological responses to a variety of environmental pollutants, such as dioxin (2,3,7, TCDD) and cigarette smoke. The purpose of this study was to determine whether cigarette smoke condensate (CSC) is capable of activating the AHR in normal human oral keratinocytes (NHOK) and inhibiting their ability to senesce. Towards this end, NHOK were isolated from human subjects and were cultured in the presence or absence of either TCDD or CSC. While neither TCDD nor CSC treatments altered the lifespan of NHOK in culture, both were capable of suppressing a culture induced premature senescence as indicated by their ability to decrease the mRNA and protein levels of the senescence markers p16 INK4a , p53, p21 and p15 INK4b . A role of the AHR in mediating these events is indicated by the observations that the TCDD and CSC-induced decreases in p15 INK4b , p16 INK4a and p53 expression was accompanied by a corresponding increase in the expression levels of the AHR target gene, CYP1A1. In addition, cotreatment with the AHR antagonist, 3′-methoxy-4′-nitroflavone (MNF) blocked the effects of TCDD and CSC on p53 and CYP1A1 expression. The findings of this study indicate that in NHOK, CSC is capable of altering a key cell fate decision, i.e., commitment to premature senescence, that is in part, dependent on the AHR. These results support the idea that progression of CSC-induced tumorigenesis may include an AHR-mediated inhibition of senescence that contributes to immortalization and agents that block the actions of the AHR may be effective components of novel cancer therapeutics.

show abstract

Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers

Cited by 139 publications

References 67 publications

Characterization of Common CYP1B1 Variants with Different Capacity for Benzo[a]pyrene-7,8-Dihydrodiol Epoxide Formation from Benzo[a]pyrene

Characterization of Common CYP1B1 Variants with Different Capacity for Benzo[a]pyrene-7,8-Dihydrodiol Epoxide Formation from Benzo[a]pyrene

Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: A population-based study

Cigarette smoke condensate and dioxin suppress culture shock induced senescence in normal human oral keratinocytes

Contact Info

Product

Resources

About