國家衛生研究院 NHRI:Item 3990099045/2398

NHRI > National Institute of Environmental Health Sciences > Ming-Tsang Wu(2000-2001) > Periodical Articles > Item 3990099045/2398

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Title:	Individual variability in the zinc inducibility of metallothionein-IIA mRNA in human lymphocytes
Authors:	Wu, MT;Demple, B;Bennett, RAO;Christiani, DC;Fan, R;Hu, H
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	The metallothionein-IIA gene ( MT-IIA) is a major member of the human MT gene family. Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that bind and detoxify heavy metals. At least two different MT-IIA polymorphisms have been identified in humans, one or both of which may affect susceptibility to metal toxicity. The purpose of this study was to investigate whether these different genotypes affect the inducibility of MT-IIA mRNA in human lymphocytes treated with zinc ( Zn), the major known inducer of MT-IIA in vitro. Fresh lymphocytes obtained from 16 healthy volunteers, aged 23-38 yr, were genotyped for the MT-IIA gene and tested for expression. A 435-bp HindIII-TaqI fragment of the MT-IIA promoter was used to probe for the two known polymorphisms ( a 7.8-kb vs. a 5.3-kb fragment, and a 1.7-kb vs. a 1.6-kb fragment). The allele frequencies of the 16 subjects were 14% for 5.3-kb allele and 19% for 1.6-kb allele. In Northern blotting experiments, MT-IIA mRNA levels were induced over a wide range of Zn concentrations during 2-h exposures; specifically, levels increased by 9- to 115-fold with exposure to 100 muM ZnCl2 and by 16- to 311-fold with exposure to 200 muM ZnCl2. However, no significant differences in MT-IIA inducibility were found between the 7.8/5.3-kb allele pair ( n = 4) and the 7.8/7.8-kb allele pair (n = 12) or between the 1.7/1.6-kb allele pair (n = 5) and the 1.7/1.7-kb allele pair (n = 11). Thus, MT-IIA is strongly inducible by Zn in human lymphocytes, but individual variations exceed those that can be attributed to the known promoter-region polymorphisms.
Keywords:	Environmental Sciences;Public, Environmental & Occupational Health;Toxicology
Date:	2000-12
Relation:	Journal of Toxicology and Environmental Health Part A: Current Issues. 2000 Dec;61(7):553-567.
Link to:	http://dx.doi.org/10.1080/00984100050194081
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1528-7394&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000165378500001
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0034672671
Appears in Collections:	[Ming-Tsang Wu(2000-2001)] Periodical Articles

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