start-ver=1.4
cd-journal=joma
no-vol=45
cd-vols=
no-issue=1
article-no=
start-page=11
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230323
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Apoptotic cell death is an important survival system for multicellular organisms because it removes damaged cells. Mutation is also a survival method for dealing with damaged cells in multicellular and also unicellular organisms, when DNA lesions are not removed. However, to the best of our knowledge, no reports have comprehensively explored the direct relationship between apoptosis and somatic cell mutations induced by various mutagenic factors.
Results Mutation was examined by the wing-spot test, which is used to detect somatic cell mutations, including chromosomal recombination. Apoptosis was observed in the wing discs by acridine orange staining in situ. After treatment with chemical mutagens, ultraviolet light (UV), and X-ray, both the apoptotic frequency and mutagenic activity increased in a dose-dependent manner at non-toxic doses. When we used DNA repair-deficient Drosophila strains, the correlation coefficient of the relationship between apoptosis and mutagenicity, differed from that of the wild-type. To explore how apoptosis affects the behavior of mutated cells, we determined the spot size, i.e., the number of mutated cells in a spot. In parallel with an increase in apoptosis, the spot size increased with MNU or X-ray treatment dose-dependently; however, this increase was not seen with UV irradiation. In addition, BrdU incorporation, an indicator of cell proliferation, in the wing discs was suppressed at 6 h, with peak at 12 h post-treatment with X-ray, and that it started to increase again at 24 h; however, this was not seen with UV irradiation.
Conclusion Damage-induced apoptosis and mutation might be coordinated with each other, and the frequency of apoptosis and mutagenicity are balanced depending on the type of DNA damage. From the data of the spot size and BrdU incorporation, it is possible that mutated cells replace apoptotic cells due to their high frequency of cell division, resulting in enlargement of the spot size after MNU or X-ray treatment. We consider that the induction of mutation, apoptosis, and/or cell growth varies in multi-cellular organisms depending on the type of the mutagens, and that their balance and coordination have an important function to counter DNA damage for the survival of the organism.
en-copyright=
kn-copyright=
en-aut-name=Toyoshima-SasataniMegumi
en-aut-sei=Toyoshima-Sasatani
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ImuraFumika
en-aut-sei=Imura
en-aut-mei=Fumika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HamatakeYuko
en-aut-sei=Hamatake
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=FukunagaAkihiro
en-aut-sei=Fukunaga
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NegishiTomoe
en-aut-sei=Negishi
en-aut-mei=Tomoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
affil-num=1
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=School of Nursing, Osaka City University
kn-affil=
affil-num=5
en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Drosophila
kn-keyword=Drosophila
en-keyword=Apoptosis
kn-keyword=Apoptosis
en-keyword=Mutation
kn-keyword=Mutation
en-keyword=Larval wing disc
kn-keyword=Larval wing disc
en-keyword=X-ray
kn-keyword=X-ray
en-keyword=Ultraviolet
kn-keyword=Ultraviolet
en-keyword=Alkylating agents
kn-keyword=Alkylating agents
en-keyword=Tobacco smoke
kn-keyword=Tobacco smoke
en-keyword=Acridine orange
kn-keyword=Acridine orange
en-keyword=BrdU
kn-keyword=BrdU
END
start-ver=1.4
cd-journal=joma
no-vol=33
cd-vols=
no-issue=3
article-no=
start-page=89
end-page=95
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=20110812
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Exposure to Cigarette Smoke Increases Urate Level and Decreases Glutathione Level in Larval Drosophila melanogaster
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Recently, 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.
en-copyright=
kn-copyright=
en-aut-name=FujiwaraMasaru
en-aut-sei=Fujiwara
en-aut-mei=Masaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HamatakeYuko
en-aut-sei=Hamatake
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=ArimotoSakae
en-aut-sei=Arimoto
en-aut-mei=Sakae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OkamotoKeinosuke
en-aut-sei=Okamoto
en-aut-mei=Keinosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SuzukiToshinori
en-aut-sei=Suzuki
en-aut-mei=Toshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NegishiTomoe
en-aut-sei=Negishi
en-aut-mei=Tomoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
affil-num=1
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=2
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=3
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=4
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=5
en-affil=
kn-affil=School of Pharmacy, Shujitsu University
affil-num=6
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
en-keyword=environmental cigarette smoke
kn-keyword=environmental cigarette smoke
en-keyword=uric acid
kn-keyword=uric acid
en-keyword=glutathione
kn-keyword=glutathione
en-keyword=oxidative stress
kn-keyword=oxidative stress
en-keyword=survival
kn-keyword=survival
en-keyword=Drosophila
kn-keyword=Drosophila
END
start-ver=1.4
cd-journal=joma
no-vol=36
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=9
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140228
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effects of Oral Administration of Non-genotoxic Hepato-hypertrophic Compounds on Metabolic Potency of Rat Liver
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=It 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.
en-copyright=
kn-copyright=
en-aut-name=FangXing
en-aut-sei=Fang
en-aut-mei=Xing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NunoshibaTatsuo
en-aut-sei=Nunoshiba
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YoshidaMidori
en-aut-sei=Yoshida
en-aut-mei=Midori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NishikawaAkiyoshi
en-aut-sei=Nishikawa
en-aut-mei=Akiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NemotoKiyomitsu
en-aut-sei=Nemoto
en-aut-mei=Kiyomitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=DegawaMasakuni
en-aut-sei=Degawa
en-aut-mei=Masakuni
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ArimotoSakae
en-aut-sei=Arimoto
en-aut-mei=Sakae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OkamotoKeinosuke
en-aut-sei=Okamoto
en-aut-mei=Keinosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TakahashiEizo
en-aut-sei=Takahashi
en-aut-mei=Eizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NegishiTomoe
en-aut-sei=Negishi
en-aut-mei=Tomoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=2
en-affil=
kn-affil=International Christian University
affil-num=3
en-affil=
kn-affil=National Institute of Health Sciences
affil-num=4
en-affil=
kn-affil=National Institute of Health Sciences
affil-num=5
en-affil=
kn-affil=School of Pharmaceutical Sciences, University of Shizuoka
affil-num=6
en-affil=
kn-affil=School of Pharmaceutical Sciences, University of Shizuoka
affil-num=7
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=8
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=9
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=10
en-affil=
kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
en-keyword=liver hypertrophic compound
kn-keyword=liver hypertrophic compound
en-keyword=metabolism
kn-keyword=metabolism
en-keyword=mutation
kn-keyword=mutation
en-keyword=Ames test
kn-keyword=Ames test
END
start-ver=1.4
cd-journal=joma
no-vol=73
cd-vols=
no-issue=1-2
article-no=
start-page=59
end-page=66
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2003
dt-pub=200311
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Alternative methods to evaluate the protective ability of sunscreen against photo-genotoxicity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Numerous epidemiological investigations show that sunlight is carcinogenic to humans and that the use of sunscreen may be effective in decreasing the risk of skin cancer. The biological activity of a sunscreen is evaluated by its ability to protect human skin from erythema as represented by a Sun Protection Factor (SPF). We propose that the sunscreen's protective effect against sunlight-induced genotoxicity, including mutation, should also be taken into account. In this study we examined the protective ability of sunscreens against natural sunlight and UV-induced genotoxicity in Drosophila somatic cells. We prepared three kinds of sunscreen samples, each with an SPF value of 20, 40 or 60 and compared their protective activities with commercial sunscreens. When a sunscreen of SPF 20, 40 or 60 was pasted on the plastic cover of a petri dish in which Drosophila larvae were exposed to the sun or UV lamps, genotoxicity decreased as the SPF of the sunscreen increased, relative to levels of genotoxicity observed in samples without sunscreen. However, the protective abilities of sunscreens were unexpectedly not so different from each other. To reveal the relationship between the protective activity of sunscreen and the wavelength of light with which larvae were irradiated through the sunscreen, we measured the transmittance of light through the petri dish cover on which the sunscreen was pasted. Effective protection was demonstrated by removing components of light whose wavelengths were below 315 nm. We suggest, that the measurement of anti-genotoxic activity and the determination of the wavelengths of light transmitted through the sunscreen should be an alternative method for evaluating the effectiveness of a sunscreen.
en-copyright=
kn-copyright=
en-aut-name=ToyoshimaMegumi
en-aut-sei=Toyoshima
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HosodaKanako
en-aut-sei=Hosoda
en-aut-mei=Kanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HanamuraMiho
en-aut-sei=Hanamura
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OkamotoKeinosuke
en-aut-sei=Okamoto
en-aut-mei=Keinosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KobayashiHiroshi
en-aut-sei=Kobayashi
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NegishiTomoe
en-aut-sei=Negishi
en-aut-mei=Tomoe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama University
affil-num=2
en-affil=
kn-affil=Okayama University
affil-num=3
en-affil=
kn-affil=Okayama University
affil-num=4
en-affil=
kn-affil=Okayama University
affil-num=5
en-affil=
kn-affil=Shiseido Research Center
affil-num=6
en-affil=
kn-affil=Okayama University
en-keyword=sunscreen
kn-keyword=sunscreen
en-keyword=sunlight
kn-keyword=sunlight
en-keyword=UVB
kn-keyword=UVB
en-keyword=somatic cell mutation
kn-keyword=somatic cell mutation
en-keyword=genotoxicity
kn-keyword=genotoxicity
en-keyword=transmittance
kn-keyword=transmittance
en-keyword=Drosophila melanogaster
kn-keyword=Drosophila melanogaster
END