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Division of Oncology, Department of Medicine, Neil Hellman Medical Research Building, Albany Medical College, Albany, New York 12208 [W. P. T., D. B. L.], and Southern Research Institute, Birmingham, Alabama 35205 [M. C. K.]
The cross-linked dinucleoside, 1-[N3-deoxycytidyl],2-[N1-deoxyguanosinyl]ethane, has been isolated from DNA which has been exposed to N,N'-bis(2-chloroethyl)-N-nitrosourea. It is probable that this structure is responsible for the interstrand cross-linking observed previously by physical methods. The modification is unique in that it cross-links DNA through two base-pairing positions and probably arises through the transfer of a chloroethyl group to one of the bases followed by a second reaction of this group with the other strand of DNA. Initial attack could be at the N3 position of deoxycytidine, the N1 position of deoxyguanosine, or possibly the O6 position of deoxyguanosine. Attack at the O6 position of deoxyguanosine would require an internal cyclization with the N1 position of deoxyguanosine before secondary reaction with the N3 position of deoxycytidine but would explain resistance to N,N'-bis(2-chloroethyl)-N-nitrosourea in cells capable of removing substituents on the O6 position of guanine.
1 Supported by Grants CA 20129 and CA 32171 from the National Cancer Institute. A preliminary report of this research has been presented (12).
2 To whom requests for reprints should be addressed.
Received 3/ 8/82. Accepted 5/ 7/82.
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