DNA-DAMAGE BY SINGULET MOLECULAR-OXYGEN, PROTECTION BY POLYAMINES ANDBIOLOGICAL EFFECT

DNA damage induced by singlet molecular oxygen (O-1(2)) and their biol ogical consequences were investigated, using the thermodissociation of the water soluble endoperoxide of 3,3'-(1,4-naphthylidene) dipropiona te (NDPO2), which produces only O-1(2), with no reactive intermediates or secondary products. By following electrophoretic mobility of singl e and double stranded DNA on agarose gels, we found that O-1(2)-treatm ent induces single and double strand breaks formation. Single strand b reaks are efficiently prevented with biomolecules, such as the polyami nes, spermine and spermidine. The lethal and mutagenic consequences of the O-1(2)-induced DNA lesions were demonstrated after introduction o f plasmid DNA into bacteria and mammalian cells. There is a clear incr ease on the mutation frequency, function of the NDPO2 concentration, w hen plasmids, single and double stranded, are introduced into monkey C OS7 cells. This suggests that O-1(2)-damaged DNA is processed in mamma lian cells by an error prone repair. The mutation spectrum reveals tha t 98% of the mutations involve G:C base pairs, thus, the high mutageni city of O-1(2) are probably due to lesions on guanines. The data suppo rts the idea that a direct bypass of guanine lesions is responsable fo r the O-1(2) mutagenicity.