TY - JOUR
T1 - Mechanism of action of the nitrosoureas—IV
T2 - Reactions of bis-chloroethyl nitrosourea and chloroethyl cyclohexyl nitrosourea with deoxyribonucleic acid
AU - Gombar, Charles T.
AU - Tong, William P.
AU - Ludlum, David B.
N1 - Funding Information:
Acknowledgements-Thisw ork was supportedb y Public Health ServiceG rant CA 20129fr om the NationalC ancer Institute( NCI), NationalI nstituteso f Health, Department of Health, Education, and Welfare. We thank Suzanne Wissel for her editorial assistance.
PY - 1980
Y1 - 1980
N2 - Calf thymus DNA was reacted with 14C-labeled bis-chloroethyl nitrosourea (BCNU), and chloroethyl cyclohexyl nitrosourea (CCNU), and the nature of the derivatives investigated in an enzymatic digest. In agreement with earlier studies on polyribonucleotides, evidence was obtained for the formation of 7-hydroxyethyldeoxyguanosine, 3-hydroxyethyldeoxycytidine and 3,N4-ethanodeoxycytidine. In addition, significant amounts of 7-aminoethylguanine were identified in the hydrolysate of DNA treated with BCNU, but not in the hydrolysate of DNA treated with CCNU. Aminoethylguanine was also formed when DNA was reacted with chloroethylamine, suggesting that BCNU produced aminoethylguanine via chloroethylamine as an intermediate. Because both BCNU and CCNU are effective antitumor agents, the formation of aminoethylguanine is probably not an important cytotoxic reaction, but it may have significance as far as mutagenic or carcinogenic activities are concerned.
AB - Calf thymus DNA was reacted with 14C-labeled bis-chloroethyl nitrosourea (BCNU), and chloroethyl cyclohexyl nitrosourea (CCNU), and the nature of the derivatives investigated in an enzymatic digest. In agreement with earlier studies on polyribonucleotides, evidence was obtained for the formation of 7-hydroxyethyldeoxyguanosine, 3-hydroxyethyldeoxycytidine and 3,N4-ethanodeoxycytidine. In addition, significant amounts of 7-aminoethylguanine were identified in the hydrolysate of DNA treated with BCNU, but not in the hydrolysate of DNA treated with CCNU. Aminoethylguanine was also formed when DNA was reacted with chloroethylamine, suggesting that BCNU produced aminoethylguanine via chloroethylamine as an intermediate. Because both BCNU and CCNU are effective antitumor agents, the formation of aminoethylguanine is probably not an important cytotoxic reaction, but it may have significance as far as mutagenic or carcinogenic activities are concerned.
UR - http://www.scopus.com/inward/record.url?scp=0018885999&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018885999&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(80)90079-9
DO - 10.1016/0006-2952(80)90079-9
M3 - Article
C2 - 7191706
AN - SCOPUS:0018885999
SN - 0006-2952
VL - 29
SP - 2639
EP - 2643
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 19
ER -