Inhalation exposure of rats and mice to 1,3-butadiene induces N6-adenine adducts of epoxybutene detected by 32P-postlabeling and HPLC.

Abstract:

:In this paper we report DNA binding of butadiene monoepoxide, a first metabolite of 1,3-butadiene catalyzed by monooxygenases. We prepared alkylated purines as marker compounds for 32-P-postlabeling and electrochemical analysis and developed methods to measure the corresponding products. The traditional postlabeling assay was modified by incorporating a solid phase extraction column and high-performance liquid chromatography (HPLC) enrichment steps to the assay prior to labeling. The final analysis of adducted N6 adenines is based on two dimensional thin-layer chromatography (TLC) and an on-line HPLC/radioactivity analysis. The qualitative and quantitative results are based on positively identified marker compounds. Alkylated N7 guanines were released from DNA by neutral thermal hydrolysis, prepurified by HPLC, and analyzed by HPLC with a sensitive electrochemical detection procedure. By using these methods, we found alkylation of calf thymus DNA exposed to butadiene monoepoxide in vitro at adenine N6 and guanine N7 sites. Analysis of lung DNA samples from mice and rats exposed to butadiene through inhalation showed that adenine N6 adducts were formed in vivo in a dose responsive manner.

authors

Koivisto P,Adler ID,Sorsa M,Peltonen K

doi

10.1289/ehp.96104s3655

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

655-7

eissn

0091-6765

issn

1552-9924

journal_volume

104 Suppl 3

pub_type

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