Formaldehyde-induced mutagenesis: a novel mechanism for its action.
A novel and unique mechanism for formaldehyde-induced mutagenesis is described which is mediated by the formation of an N6-substituted adenine ribonucleoside analogue, N6-hydroxymethyl adenosine, after an in vitro reaction of formaldehyde with adenosine. This type of ribonucleoside analogue (the deoxyribose derivative is ineffective) exhibits a powerful and remarkable germ-cell-stage-specific mutagenic effect in male Drosophila larvae, apparently by interfering with DNA repair. Circumstantial evidence is presented which indicates that the analogue most probably acts by its utilisation in the synthesis of diadenosine tetraphosphate (Ap4A) to form an antimetabolite(s) of Ap4A which subsequently interferes with Ap4A-mediated intracellular events, amongst which an effect on DNA repair would appear to be its mutagenic mechanism of action.
D000227:Adenine Nucleotides / Q000096:biosynthesis; D000241:Adenosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects; D015226:Dinucleoside Phosphates; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology* / Q000633:toxicity; D007814:Larva; D008297:Male; D008322:Mammals; D008647:Mesocricetus; D051379:Mice; D009154:Mutation; D009866:Oogenesis / Q000187:drug effects; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D005557:Formaldehyde; D011064:Poly Adenosine Diphosphate Ribose; C046518:N,N'-methylenebis(adenosine diphosphate); C020733:diadenosine tetraphosphate; D000244:Adenosine Diphosphate; C046517:N(6)-hydroxymethyladenosine; D011065:Poly(ADP-ribose) Polymerases; D000241:Adenosine