Photobiological studies with dioxetanes in isolated DNA, bacteria, and mammalian cells.
1,2-Dioxetanes, efficient chemical sources of triplet excited carbonyl compounds, were observed to be genotoxic in isolated DNA, bacteria, and cultured mammalian cells. In superhelical DNA of bacteriophage PM2, various alkyl- and hydroxyalkyl-substituted dioxetanes (1) induced predominantly endonuclease-sensitive base modifications and only few single strand breaks. With a specific endonuclease a small fraction of the base modifications was identified as pyrimidine dimers. The psoralen dioxetane (2a) or PsD bound photochemically to calf thymus DNA at the alpha-pyrone ring of psoralen (fluorescence measurements). Photobinding was also observed when calf thymus DNA was incubated with psoralen and 3-hydroxymethyl-3,4,4-trimethyl-1,2-dioxetane. In Syrian hamster embryo fibroblasts and HL-60 cells, dioxetanes induced DNA single strand breaks. The alkyl- and hydroxyalkyl-substituted dioxetanes 1 and 2 were efficiently inactivated by cysteine, glutathione, ascorbic acid, tocopherol, NADH and FADH2. While dioxetanes 1 and 2 were not mutagenic in Salmonella typhimurium strain TA100, benzofuran dioxetanes 3 exhibited substantial effects. Further data imply that presumably a mutagenic intermediate with a lifetime of a few minutes is produced from the benzofuran dioxetane.
Adam
W
W
Institute of Organic Chemistry, University of Würzburg, Federal Republic of Germany.
Beinhauer
A
A
Mosandl
T
T
Saha-Möller
C
C
Vargas
F
F
Epe
B
B
Müller
E
E
Schiffmann
D
D
Wild
D
D
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D006801:Humans; D009153:Mutagens / Q000528:radiation effects*; D010777:Photochemistry
D006571:Heterocyclic Compounds; D009153:Mutagens; D004247:DNA