Modification of DNA bases by anthralin and related compounds.
Modification of bases in calf thymus DNA by treatment with the antipsoriatic drug anthralin was studied. The products of DNA bases were identified and their yields measured by gas chromatography-mass spectrometry with selected ion monitoring. Treatment of calf thymus DNA with anthralin significantly enhanced the amount of modified bases above control levels. Purine bases were modified to products identical with those known to be typical of DNA damage induced by hydroxyl radicals. The yields of Fapy-adenine, 8-hydroxyadenine, Fapy-guanine, and 8-hydroxyguanine were maximally increased at an anthralin concentration of 75 microM. A variety of structural analogues of anthralin were also tested at 75 microM were either weaker or stronger hydroxylating agents. It is likely that damage to DNA bases induced by anthrones contributes to their antiproliferative activity. The pharmacological implications of these characteristics of the action of anthralin on DNA bases are discussed.
Müller
K
K
Institute of Pharmacy, University of Regensburg, Germany.
Leukel
P
P
Mayer
K K
KK
Wiegrebe
W
W
D000225:Adenine / Q000031:analogs & derivatives / Q000032:analysis; D000818:Animals; D000875:Anthralin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003879:Dermatologic Agents / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006900:Hydroxylation; D011743:Pyrimidines / Q000032:analysis
D003879:Dermatologic Agents; D011743:Pyrimidines; C071023:2,6-diamino-4-hydroxy-5-formamidopyrimidine; C002992:8-hydroxyadenine; C039544:4,6-diamino-5-N-formamidopyrimidine; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D000225:Adenine; D000875:Anthralin