Acta Medica Okayama1880-70463332011Exposure to Cigarette Smoke Increases Urate Level and Decreases Glutathione Level in Larval Drosophila melanogaster8995ENMasaruFujiwaraYukoHamatakeSakaeArimotoKeinosukeOkamotoToshinoriSuzukiTomoeNegishiRecently, we reported experimental evidence to support the notion that in Drosophila melanogaster, urate is involved in defense against toxic effects of environmental cigarette smoke (ECS). To obtain further information pertaining to the defense mechanisms involving urate and other antioxidants, the present study measured the levels of urate, its precursors and glutathione, and SOD activity in larval flies of wild-type strains (Oregon-R and Canton-S) and two urate-null mutant strains (ma-l and ry1) following exposure to ECS for various durations. In both wild type strains, unlike the case in either of the mutant strains, the urate level significantly increased above the basal level in a manner dependent on the duration of ECS exposure. Similar increases in the level of urate precursors were found in Canton-S and in both of the urate-null strains. There was a slight increase in glutathione level above the control level following ECS exposure for a short time, followed by an exposure-dependent decrease to less than 60% of the control level within the exposure range used in all of the four strains. On the other hand, no appreciable change was found in the SOD activity prior to or following ECS exposure, irrespective of the strain examined. In terms of the survival of treated larvae to adulthood under the conditions used for the measurements of urate and others, it was found that wild-type strain Canton-S was as sensitive as the urate-null mutant strains and clearly more sensitive than wild-type strains Oregon-R and Hikone-R. This was so despite the fact that, compared with Oregon-R, Canton-S contained urate at relatively higher levels prior to and following ECS exposure, and that the glutathione levels in Canton-S prior to and following treatment were comparable with those in other strains. These results are discussed with respect to the involvement of urate and glutathione in defense against the toxicity of ECS and the possible existence of another defense mechanism which is deficient in the Canton-S strain.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1880-70463612014Effects of Oral Administration of Non-genotoxic Hepato-hypertrophic Compounds on Metabolic Potency of Rat Liver19ENXingFangTatsuoNunoshibaMidoriYoshidaAkiyoshiNishikawaKiyomitsuNemotoMasakuniDegawaSakaeArimotoKeinosukeOkamotoEizoTakahashiTomoeNegishiIt remains uncertain why non-genotoxic compounds that result in liver hypertrophy cause liver tumors. In an effort to resolve this issue, we examined whether liver post-mitochondrial fraction (S9) prepared from rats treated with non-genotoxic compounds affected the genotoxicity of pro-mutagens. Known hepatotoxic compounds, such as piperonyl butoxide (PBO), decabromodiphenyl ether (DBDE), beta-naphthoflavone (BNF), indole-3-carbinol (I3C) and acetaminophen (AA), were orally administered to male and female F344 rats at doses sufficient to cause liver hypertrophy. Rats received diets containing each test compound for 3 days, 4 weeks or 13 weeks, and were then kept for 4 weeks without the test chemical. S9 prepared from the livers of each group was used for the Ames test with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), benzo[a]pyrene (BaP) and N-nitrosodimethylamine (NDMA). In both sexes, liver hypertrophy was observed following administration of all test compounds, and was then reversed to the control state when administration ceased. The mutagenicity of MeIQx, BaP and NDMA increased with the use of S9 derived from rats treated with non-genotoxic compounds other than AA. DBDE administration had a marked effect on the mutagenicity of BaP (over a 30-fold increase in females) and NDMA (about a 20-fold increase in males). To estimate the involvement of metabolic enzymes in the alteration of mutagenicity, we measured the activity of ethoxyresorufin-O-deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) (phase I enzymes), and UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST) (phase II enzymes) in each S9 sample. The activity of phase I enzymes increased, even at the 3rd day following administration, and then decreased gradually, except in the case of AA, while the activity of phase II enzymes increased slightly. These results suggest that non-genotoxic hepato-hypertrophic compounds may be partly involved in carcinogenesis by modulating the metabolism of pre-carcinogens incorporated from the environment, in a manner that is dependent on sex and pre-incorporated chemicals.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1989環境変異原物質に対する活性修飾とその機構ENNo potential conflict of interest relevant to this article was reported.