title: Suppressive effect of post- or pre-treatment of aspirin metabolite on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster.
abstract: In our previous paper, we found that aspirin suppressed in a somatic mutation and recombination test (SMART) of mitomycin C (MMC) in Drosophila melanogaster. In order to reveal the mechanism of bio-antimutagenicity and/or preventive effect of aspirin, we evaluated the suppressive ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA) and 2,3-dihydroxybenzoic acid (DHBA), in SMART in D. melanogaster using post- and pre-treatments. As for the post-treatment, SA reduced the numbers of large single and twin spots. GA reduced the small single and large single spots, and GUA reduced the single spots, large single and twin spots. The inhibition of GUA is slightly stronger than that of any other metabolites; the inhibition percentage is 49 at the dose of 5 mg/bottle. On the other hand, as for the pre-treatment, aspirin, SUA, GA and DHBA reduced the numbers of small single spots. SUA, GE and DHBA reduced the number of large single spots. Aspirin and its metabolites did not reduce the number of twin spots. The results of the present study suggest that SA, GA and GUA repair or replicate DNA-damage by MMC and SUA, GA, GUA and DHBA prevent DNA-damage by MMC. It is suggested that secondary cancer is prevented by aspirin post-treatment without losing the medicinal effectiveness (anti-tumor activity). Therefore, we consider there are effective doses and/or administration timing of aspirin and MMC to prevent secondary cancer.
authors.affiliation: Department of Hygienics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan. niikawam@tim.hi-ho.ne.jp
authors.forename: Miki
authors.initials: M
authors.lastname: Niikawa
authors.forename: Seizai
authors.initials: S
authors.lastname: Shin
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005260:Female; D005841:Gentisates / Q000494:pharmacology; D006626:Hippurates / Q000494:pharmacology; D062385:Hydroxybenzoates / Q000494:pharmacology; D008297:Male; D016685:Mitomycin / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D011995:Recombination, Genetic / Q000187:drug effects*; D020156:Salicylic Acid / Q000494:pharmacology
chemical_list: D016587:Antimutagenic Agents; D005841:Gentisates; D006626:Hippurates; D062385:Hydroxybenzoates; D009153:Mutagens; C016471:gentisuric acid; C000693:salicylurate; D016685:Mitomycin; C009135:2,3-dihydroxybenzoic acid; D020156:Salicylic Acid; D001241:Aspirin; C010925:2,5-dihydroxybenzoic acid