Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans

Landi, Maria Teresa; Bertazzi, P.A.; Shields, Paula; Clark, George C.; Lucier, George W.; Garte, Seymour; Cosma, Greg; Caporaso, Neil E.

doi:10.1097/00008571-199410000-00002

Cited by 186 publications

(105 citation statements)

References 0 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Different inducibility has been reported among the allelic variants of CYP1A1 (30,31). For example, CYP1A1*2A and CYP1A1*2B harboring a 3801T>C transition, resulting in a new MspI restriction endonuclease site, are associated with a highly inducible phenotype of the enzyme (32). However, the observed superior activity of the cells expressing CYP1A1*2C (I462V) for hydroxylations of AF could not be explained by differential enzyme expression or inducibility because (a) real-time RT-PCR and Western blot did not detect any apparent differences in mRNA and protein expression levels of CYP1A1 among the selected stable clones expressing CYP1A1*1, CYP1A1*2C, and CYP1A1*4 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone

Zheng

Sha

Liu

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Aminoflavone (AF), a clinically investigational novel anticancer agent, requires sequential metabolic activation by CYP1A1 and SULT1A1 to exert its antitumor activities. The purpose of this study was to determine the functional significance of common polymorphisms of human CYP1A1 and SULT1A1 on the metabolism and cytotoxicity of AF. To this end, Chinese Hamster V79 cells were genetically engineered to stably express human CYP1A1*1 (wild-type), CYP1A1*2C (I462V), or CYP1A1*4 (T461N) and coexpress human CYP1A1*1 with human SULT1A1*1 (wild-type), SULT1A1*2 (R213H), or SULT1A1*3 (M223V). The metabolism and cytotoxicity of AF were evaluated in these cellular models. All common variants of CYP1A1 and SULT1A1 were actively involved in the metabolic activation of AF, but with a varying degree of activity. Whereas CYP1A1 I462V variant exhibited a superior activity (mainly caused by a significantly higher V max ) for hydroxylations of AF, expression of different CYP1A1 variants did not confer cell differential sensitivity to AF. The cells coexpressing CYP1A1*1 with SULT1A1

show abstract

Section: Discussionmentioning

confidence: 99%

Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone

Zheng

Sha

Liu

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Genotypic variation resulting in a phenotype that increases 2-OH may decrease risk of carcinogenesis by two possible mechanisms: competitively reducing potentially genotoxic 4-OH intermediates and increasing 2-OH intermediates, which can be methylated to 2-MeO-E2, an antiangiogenic metabolite (26). Functional studies have shown increased enzyme activity with m1 ''C,'' m2 Val 462 , and m3 ''C'' alleles and reduced activity with m4 Asn 461 allele (27)(28)(29)(30). Similar to results of previous studies, we observed no association between the CYP1A1 m1, m2, and m4 polymorphisms and epithelial ovarian cancer (9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

Ovarian Cancer Risk and Polymorphisms Involved in Estrogen Catabolism

Holt

Rossing

Malone

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Polymorphisms within genes responsible for estrogen catabolism could alter cellular levels of genotoxic 4-hydroxylated catechol estrogens and antiangiogenic 2-methoxyestradiol, thus influencing risk of developing ovarian cancer. We carried out a population-based case-control study of 310 epithelial ovarian cancer cases and 585 controls in African-American and Caucasian women ages 35 to 54 years from Seattle, Atlanta, and Detroit metropolitan areas. Subjects were interviewed and genotyped for CYP1A1 m1, m2, m3, and m4; CYP1B1

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

Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans

Cited by 186 publications

References 0 publications

Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone

Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone

Ovarian Cancer Risk and Polymorphisms Involved in Estrogen Catabolism

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

Contact Info

Product

Resources

About