Identification of 7-(2-hydroxyethyl)guanine as a product of alkylation of calf thymus DNA with clomesone.
Evidence at the molecular level is presented in support of alkylation of O6-guanine moieties of DNA as the mechanism of cytotoxicity of Clomesone to HT-29 cells and consists in the isolation and identification of a product resulting from alkylation of calf thymus DNA with Clomesone, followed by depurination to yield 7-(2-hydroxyethyl)guanine, whose formation is reasonably explained by O6-guanine chloroethylation followed by intramolecular alkylation at N7 of guanine and subsequent hydrolysis to the hydroxyethylguanine.
Struck
R F
RF
Southern Research Institute, Birmingham, AL 35255.
Alexander
J A
JA
McCain
D M
DM
Shealy
Y F
YF
Rose
L M
LM
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000302:isolation & purification; D006868:Hydrolysis; D008698:Mesylates / Q000494:pharmacology*; D008745:Methylation; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism*
D000970:Antineoplastic Agents; D008698:Mesylates; C041189:clomesone; C035018:N(7)-hydroxyethylguanine; D006147:Guanine; C030920:6-hydroxyethylguanine; D004247:DNA