DNA strand breakage by hydroxyphenyl radicals generated from mutagenic diazoquinone compounds.
The mutagenic diazoquinone compounds p-diazoquinone (p-DQ), o-diazoquinone (o-DQ) and 3-diazo-N-nitrosobamethan (D-BM) cleaved the phosphodiester bond of lambda DNA, phi X174 RFI DNA and M13mp8ss DNA. p-DQ also cleaved the phosphodiester bond of bis(p-nitrophenyl)phosphate. The breakage of the phosphodiester bond was inhibited by the antioxidant butyl hydroxyanisole (BHA), ethanol, the spin trapping agent DMPO, cysteine and 2-mercaptoethanol. While incubation of p-DQ and o-DQ alone gave p-hydroquinone and catechol, respectively, incubation of these compounds in the presence of BHA and ethanol gave phenol in large yields. Incubation of p-DQ and o-DQ with the spin trapping agents DMPO and PBN gave spin adducts assignable as p- and o-hydroxyphenyl adducts, respectively. The breakage of the phosphodiester bond of DNA by the diazoquinone compounds is suggested to be due to the hydroxyphenyl radicals generated during incubation.
Kato
T
T
Tokyo College of Pharmacy, Japan.
Kojima
K
K
Hiramoto
K
K
Kikugawa
K
K
D001435:Bacteriophages / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects*; D004279:DNA, Viral / Q000187:drug effects; D004983:Ethanolamines / Q000031:analogs & derivatives* / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010627:Phenethylamines; D011809:Quinones / Q000633:toxicity*; D013696:Temperature
D004279:DNA, Viral; D004983:Ethanolamines; D009153:Mutagens; D010627:Phenethylamines; D011809:Quinones; C051613:3-diazo-N-nitrosobamethan; C055898:2-diazoquinone; C055897:4-diazoquinone