The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant.

The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Research Abstract Details 

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The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Abstract Text:

Shou-Lin Wang,Xiao-Yang He,Jian Shen,Jia-Sheng Wang,Jun-Yan Hong,

Cytochrome P450 2A13 (CYP2A13), an enzyme predominantly expressed in human respiratory tissues, is highly efficient for the metabolic activation of two suspected human lung carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and aflatoxin B1 (AFB1). Functional genetic polymorphisms of CYP2A13 may therefore be an important factor in human susceptibility to related lung cancers. Among the reported CYP2A13 polymorphisms with missense variations, only CYP2A13*2 variant (containing either a single or double variation of R25Q and R257C) was studied for its NNK-metabolizing activity. The present study demonstrated that there was no remarkable difference in AFB1- and NNK-induced toxicity between the Flp-In Chinese Hamster Ovary (CHO) cells stably expressing wild-type CYP2A13 and the cells expressing the individual polymorphic variants R25Q, D158E, R257C, R25Q/R257C, V323L, F453Y, and R494C. In contrast, cells transfected with R101Q variant complementary DNA (cDNA), same as the vector control cells, showed no significant death even at highest concentrations of AFB1 (10microM) and NNK (200microM). This result correlated with the lack of CYP2A13 protein in the R101Q-CHO cells, although the genomic integration of transfected R101Q cDNA and the expression of R101Q messenger RNA were clearly demonstrated in these stable transfectants. Consistent with the possibility that the variation might reduce the protein stability, R101Q variant protein expressed in insect cells showed a loss of P450 peak and coumarin 7-hydroxylase activity as well as an increased susceptibility to limited protein digestion. Thus, the R101Q polymorphic change results in a null allelic variant of CYP2A13. Our results should be useful in designing and interpreting molecular epidemiological studies related to CYP2A13 genetic polymorphisms.

The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Publishing Authors By Initials

SL Wang,XY He,J Shen,JS Wang,JY Hong,

For similar genetic phenomena: variation (genetics) research abstracts see: genetic phenomena: variation (genetics) research

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The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Toxicological sciences : an official journal of th

VOLUME: 94

Page Numbers: 38-45

Journal Abbreviation: Toxicol. Sci.

ISSN: 1096-6080

DAY: 17

MONTH: 08

YEAR: 2006

The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9805461

The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Keywords Mesh Terms:

KEYWORDS: Variation (Genetics)

MESH TERMS: genetics

Chemical & Substance for Abstract: The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Information

Substance Name: FLP recombinase

Registry Number: EC 2.7.7.-

Grant and Affiliation Information for The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant.

AFFILIATION: School of Public Health/Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: R01-ES10048

ACRONYM: ES

MEDLINETA: Toxicol Sci

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