2-(p-Nitrophenyl)-2'-deoxyadenosine, a new type of mutagenic nucleoside.
A crude preparation of 2-phenyladenosine was found to be mutagenic in the Ames Salmonella assay. In the purification of this preparation, it was revealed that 2-phenyladenosine itself was nonmutagenic but that 2-(m- and p-nitrophenyl)-adenosines (5m,p) contaminating the sample were the mutagenic principles. A structure-activity relationship study was carried out, and it was found that 5p, 2-(p-nitrophenyl)-adenine (7p), and 2-(p-nitrophenyl)-2'-deoxyadenosine (15p) were strongly mutagenic toward S. typhimurium TA98 and TA100 without metabolic activation, the potency being in the order 15p greater than 7p greater than 5p. The potency of 15p in TA98 was one order of magnitude greater than that of 4-nitroquinoline N-oxide. 15p also showed mutagenicity in the mouse cell line FM3A in culture.
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
A
A
Matsuda
Y
Y
Ohara
T
T
Kakutani
K
K
Negishi
Y
Y
Wataya
H
H
Hayatsu
T
T
Ueda
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003839:Deoxyadenosines; D007202:Indicators and Reagents; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D003839:Deoxyadenosines; D007202:Indicators and Reagents; D009153:Mutagens; D009705:Nucleosides; C051675:2'-deoxy-2-(4-nitrophenyl)adenosine; D000241:Adenosine