A 7-hydroxymethyl sulphate ester as an active metabolite of the carcinogen, 7-hydroxymethylbenz[a]anthracene.

Abstract:

:7-Hydroxymethylbenz[a]anthracene (7-HBA) showed potent mutagenicity towards Salmonella typhimurium TA 98 in the presence of untreated rat liver cytosol fortified with the PAPS-generating system, sodium sulphate and ATP. No mutagenic activity was observed either when the cytosol was boiled or when sodium sulphate or ATP was omitted from the assay medium. A highly reactive sulphate ester of 7-HBA was isolated and identified from the medium. It had a half-life of 3.5 min at 37 degrees C and pH 7.4 in water and showed potent, intrinsic mutagenicity towards TA 98. The mutagenicity of 7-HBA sulphate was almost completely retarded in the presence of the cytosol and glutathione. From the biological systems containing glutathione a non-mutagenic and stable glutathione conjugate was isolated that was assigned as S-(benz[a]anthracen-7-yl)methylglutathione. 7-HBA sulphate covalently bound to calf thymus DNA and cytosolic proteins. A fluorospectroscopic study indicated that the carcinogen bound to the biomacromolecules through its 7-methylene group with loss of a sulphate anion as a leaving group.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Watabe T,Hakamata Y,Hiratsuka A,Ogura K

doi

10.1093/carcin/7.2.207

subject

Has Abstract

pub_date

1986-02-01 00:00:00

pages

207-14

issue

2

eissn

0143-3334

issn

1460-2180

journal_volume

7

pub_type

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