Mechanism of benzo(a)pyrene diol epoxide induced deoxyribonucleic acid strand scission

Journal Article · Tue Jan 01 00:00:00 EST 1980 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00558a009· OSTI ID:6319215

Gamper, H B; Bartholomew, J C; Calvin, M

Approximately 1% of (+-) -7..beta.., 8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BaP-diol epoxide) DNA alkylation sites rearrange with strand scission at neutral pH. Phosphotriester hydrolysis and depurination/depyrimidination strand scission were critically examined as possible mechanisms for this phenomenon. No direct evidence was obtained for nicking occurring through phosphotriester hydrolysis. Studies with model substrates, including dibutyl phosphate, DNA homopolymers, and TMV RNA, indicated that if BaP-diol epoxide forms phosphotriesters in DNA or RNA, they do not hydrolyze with strand scission. Besides apurinic/apyrimidinic sites, a second alkali-sensitive rearrangement product was present in BaP-diol epoxide modified DNA. These latter sites accumulated with time and after 24 h accounted for as much as 4% of the initial alkylation events.

• Research Organization: Univ. of California, Berkeley
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 6319215
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 19; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ADDUCTS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
CONDENSED AROMATICS
DECOMPOSITION
DNA
HYDROCARBONS
HYDROLYSIS
LYSIS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
SOLVOLYSIS
STRAND BREAKS