CHEMICAL SYNTHESIS AND DETECTION OF THE CROSS-LINK 1-[N3-(2'-DEOXYCYTIDYL)]-2-[N1-(2'-DEOXYGUANOSINYL)]ETHANE IN DNA REACTED WITH 1-(2-CHLOROETHYL)-1-NITROSOUREA
被引:46
作者:
BODELL, WJ
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机构:UNIV CALIF SAN FRANCISCO,SCH MED,BRAIN TUMOR RES CTR,SAN FRANCISCO,CA 94143
BODELL, WJ
PONGRACZ, K
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机构:UNIV CALIF SAN FRANCISCO,SCH MED,BRAIN TUMOR RES CTR,SAN FRANCISCO,CA 94143
PONGRACZ, K
机构:
[1] UNIV CALIF SAN FRANCISCO,SCH MED,BRAIN TUMOR RES CTR,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,SCH MED,DEPT NEUROL SURG,SAN FRANCISCO,CA 94143
[3] UNIV CALIF SAN FRANCISCO,SCH MED,DEPT RADIAT ONCOL,SAN FRANCISCO,CA 94143
We have synthesized 1-[N3-(2'-deoxycytidyl)]-2-[N1-(2'-deoxyguanosinyl)]ethane and confirmed its structure by ultraviolet and high-resolution mass spectrometry. Treatment of calf thymus DNA with [H-3](2-chloroethyl)-l-nitrosourea resulted in the formation of at least 13 DNA alkylation products that were separated by HPLC. 1-[N3-(2'-Deoxycytidyl)]-2-[N1-(2'-deoxyguanosinyl)]ethane was a minor product, accounting for 3.4% of the total DNA alkylation. The DNA cross-link 1,2-di-N7-guanylethane was formed to a similar extent (3.2%). Other minor alkylation products were O6-(2-hydroxyethyl)deoxyguanosine (1.5%) and N1-(2-hydroxyethyl)deoxyguanosine (3.8%). The principal alkylation products formed by 1-(2-chloroethyl)-1-nitrosourea (CNU) treatment of DNA were N7-(2-hydroxyethyl)guanine (36.4%), N7-(2-chloroethyl)guanine (14.6%), and phosphotriesters (26.1%). The development of analytical procedures to measure DNA alkylation products after treatment with CNU will allow us to investigate factors influencing their formation and repair.