PMID- 9348440
OWN - NLM
STAT- MEDLINE
DCOM- 19971120
LR  - 20181016
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 10
IP  - 10
DP  - 1997 Oct
TI  - Adenine adducts with diepoxybutane: isolation and analysis in exposed calf thymus 
      DNA.
PG  - 1171-9
AB  - 1,3-Butadiene (BD) is a high-volume industrial chemical and a common 
      environmental pollutant. Although BD is classified as a "probable human 
      carcinogen", only limited evidence is available for its tumorigenic effects in 
      occupationally exposed populations. Animal studies show a surprisingly high 
      sensitivity of mice to the carcinogenic effects of BD compared to rats 
      (approximately 10(3)-fold), making interspecies extrapolations difficult. 
      Identification and quantitation of specific BD-induced DNA adducts are important 
      for improving our understanding of the mechanisms of BD biological effects and 
      for explaining the observed species differences. Covalent binding of BD to DNA is 
      probably due to its two epoxy metabolites: 3,4-epoxy-1-butene (EB) and 
      1,2:3,4-diepoxybutane (DEB). Both EB and DEB are direct mutagens producing 
      frameshift and point mutations at both A:T and G:C base pairs. DEB is 100 times 
      more mutagenic than EB and is found in quantity only in tissues of the most 
      sensitive species (mouse). This has led to the suggestion that the higher 
      sensitivity of mice to BD could be due to greater exposure to DEB. The present 
      work was initiated in order to isolate and structurally characterize DEB-induced 
      adenine adducts. The adducts were formed by reacting DEB with free adenine (Ade), 
      2'-deoxyadenosine (2'-dAdo), and calf thymus DNA followed by HPLC separation and 
      analysis of the products by UV spectrophotometry, electrospray ionization mass 
      spectrometry, and nuclear magnetic resonance. The adenine reaction resulted in 
      three products which were identified as N-3-, N-7-, and 
      N-9-(2'-hydroxy-3',4'-epoxybut-1'-yl)adenine. These adducts underwent 
      acid-catalyzed hydrolysis to their corresponding 
      (2',3',4'-trihydroxybut-1'-yl)adenines upon heating or storage. The 2'-dAdo 
      reaction with DEB followed by acid hydrolysis yielded a single adduct, 
      N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-DEB-Ade). N-3-DEB-Ade and N6-DEB-Ade 
      were also found in hydrolysates of calf thymus DNA exposed to DEB. The amounts of 
      N-3-DEB-Ade (13/10(3) normal Ade) and N6-DEB-Ade (5/10(3) normal Ade) were 
      slightly lower than those of the corresponding EB-induced adducts in similar 
      experiments, suggesting comparable reactivity of the two epoxy metabolites of BD 
      toward adenine in DNA. The findings of this study provide a basis for future 
      analyses of BD-induced adenyl DNA adducts in vitro and in vivo.
FAU - Tretyakova, N
AU  - Tretyakova N
AD  - Department of Environmental Sciences and Engineering, University of North 
      Carolina, Chapel Hill 27599, USA.
FAU - Sangaiah, R
AU  - Sangaiah R
FAU - Yen, T Y
AU  - Yen TY
FAU - Gold, A
AU  - Gold A
FAU - Swenberg, J A
AU  - Swenberg JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (DNA Adducts)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Mutagens)
RN  - 60OB65YNAB (diepoxybutane)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/*metabolism
MH  - Animals
MH  - Cattle
MH  - DNA Adducts/*analysis
MH  - Epoxy Compounds/*metabolism
MH  - Magnetic Resonance Spectroscopy
MH  - Mutagens/*metabolism
EDAT- 1998/02/12 00:00
MHDA- 1998/02/12 00:01
CRDT- 1998/02/12 00:00
PHST- 1998/02/12 00:00 [pubmed]
PHST- 1998/02/12 00:01 [medline]
PHST- 1998/02/12 00:00 [entrez]
AID - tx9700681 [pii]
AID - 10.1021/tx9700681 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 1997 Oct;10(10):1171-9. doi: 10.1021/tx9700681.