Adducts from the reaction of O,O'-diacetyl or O-acetyl derivatives of the carcinogen 4-hydroxyaminoquinoline 1-oxide with purine nucleosides

Abstract

The diacetyl derivative of 4-hydroxyaminoquinoline 1-oxide (4-HAQO), the proximate carcinogen of 4-nitroquinoline 1-oxide, was reacted in vitro with purine nucleosides to give five adducts (three with guanosine and two with adenosine). The same nucleoside modifications were also obtained with a monoacetyl derivative of 4-HAQO which is probably 4-acetoxyaminoquinoline 1-oxide. The structure of the major adduct (the so-called dG III) was identified as N-(deoxyguanosin-C8-yl)-4-aminoquinoline 1-oxide. The isolation of this adduct from the 4-HAQO-modified DNA in vivo provides strong support for the hypothesis that the acetyl derivatives of 4-HAQO constitute a good model for the ultimate carcinogen.