INDUCTION OF RESPIRATION‐DEFICIENT MUTANT OF <i>SACCHAROMYCES CEREVISIAE</i> BY CARCINOGENIC AGENT, 4‐NITROQUINOLINE N‐OXIDE AND THE EXISTENCE OF TOXOHORMONE‐LIKE FACTOR IN THE MUTANT

Mifuchi, Ichiji; Morita, Tamotsu; Yanagihara, Yasutake; Hosoi, Masaharu; Nishida, Mikio

doi:10.1111/j.1348-0421.1963.tb00244.x

Cited by 15 publications

(3 citation statements)

References 17 publications

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“…The cause of the high induction rate by aged MB is now being studied. As reported in previous papers (9,10), the induction rate of RD mutants by 4-NQO approached the maximum after 2 to 4 hours treatment, but it required at least 20 hours treatment with AF to attain the maximum induction rate of RD mutants. Consequently, resting yeast cells were treated with AF mixed with MB for 20 hours.…”

Section: Methodssupporting

confidence: 83%

EFFECT OF METHYLENE BLUE ON THE ACTION OF 4‐NITROQUINOLINE N‐OXIDE AND ACRIFLAVINE IN INDUCING RESPIRATION‐DEFICIENT MUTANTS OF SACCHAROMYCES CEREVISIAE

Morita

Mifuchi

1965

Japanese Journal of Microbiology

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Since a respiration-deficient(RD) mutant of yeast was first obtained by Ephrussi et al. (2) by treatment with acriflavine(AF) and named ' petite colonie ' mutant, others have been induced by many basic dyes'13), enzyme inhibitors(26), heavy metal salts(8), and physical effects such as ultraviolet irradiation (23) and heat shock(27).In previous papers(9,10) we reported that a carcinogenic agent, 4-nitroquinoline N-oxide(4-NQO), could induce an RD mutant which was seemingly like the mutant induced by AF. From the viewpoint of induction rate and the time required for the induction of RD mutants, the effects of 4-NQO and AF were unlike. The mutants produced by these two agents differed in their cytochrome content and in enzyme activities such as catalase, succinic dehydrogenase, lactic dehydrogenase, etc. (12). Consequently, it was thought that the mechanisms of the induction of RD mutants by both agents might be different.Extensive studies (7,14,15,17,24) on the mechanism of the induction of RD mutants with AF have been made which suggest the elimination of cytoplasmic elements and the change of nucleic acid base components as the action of AF. Nagai (15) found that the induction of RD mutants by AF was counteracted by methylene blue and toluidine blue, and from his results he suggested that AF exerted its RDinducing action in a certain specific mode of binding between the dye molecules and receptor material of yeast cells.The present paper deals with the difference in the effect of methylene blue on the induction of RD mutants by 4-NQO and AF. MATERIALS AND METHODS

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Section: Methodssupporting

confidence: 83%

EFFECT OF METHYLENE BLUE ON THE ACTION OF 4‐NITROQUINOLINE N‐OXIDE AND ACRIFLAVINE IN INDUCING RESPIRATION‐DEFICIENT MUTANTS OF SACCHAROMYCES CEREVISIAE

Morita

Mifuchi

1965

Japanese Journal of Microbiology

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“…A cytoplasmic mutagenic effect has also been reported for MNU on sunflower plastids (Beletskii, Razoriteleva & Zhdanov, 1969) as well as for the carcinogenic N-methyl-N'-nitro-N-nitrosoguanidine on yeast (Nordstrom, 1967) and on Neuro8pora cra8sa (Bertrand & Pittenger, 1968). Likewise, 4-nitroquinoline 1-oxide and several of its carcinogenic derivatives induce respiration deficiency in yeast cells (Mifuchi, Morita, Yamagihara, Hosoi & Nishida, 1963;Nagai, 1969).…”

Section: Discussionmentioning

confidence: 89%

Preferential alkylation of mitochondrial deoxyribonucleic acid by N-methyl-N-nitrosourea

Wunderlich

Schütt

Böttger

et al. 1970

Biochemical Journal

124

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The reaction of the carcinogen N-methyl-N-nitrosourea with mitochondrial DNA from various rat tissues was examined in vivo and in vitro. After incubation of isolated mitochondria or cell nuclei with N[(14)C]-methyl-N-nitrosourea in vitro and subsequent isolation and purification of the DNA the specific radioactivity of the mitochondrial DNA was 3-7 times that of the nuclear DNA. The incorporation of (14)C into embryonic mitochondrial DNA in vitro was about twice that into the liver mitochondrial DNA. Identical incorporation rates, however, were found for the reaction of isolated mitochondrial DNA or nuclear DNA respectively with N[(14)C]-methyl-N-nitrosourea. After intraperitoneal injection of 43.3-58.5mg of N[(14)C]-methyl-N-nitrosourea/kg body wt. to adult rats the labelling of the mitochondrial DNA was on average 5 times that of the nuclear DNA. A smaller specific labelling was observed for the ribosomal RNA, transfer RNA, and mitochondrial RNA as well as for the mitochondrial protein as compared with the mitochondrial DNA. After hydrolysis of the alkylated nucleic acids with hydrochloric acid, fractionation was carried out on Dowex 50 cation-exchange columns. In most experiments 70-80% of the input (14)C radioactivity was eluted in the 7-methylguanine fraction. The preferential alkylation of the mitochondrial DNA by N-methyl-N-nitrosourea in situ is discussed in connexion with the cytoplasmic-mutation hypothesis of carcinogenesis.

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“…When compared with Qs, whose genotoxicity involves formation of an enamine epoxide such as Q and 4‐MeQ, little is known on the importance of group substitutions on mutagenicity of 4‐NQO. Mifuchi et al () studied different 4‐NQO analogs and found that 2‐methyl derivative of 4‐NQO was as potent as the same 4‐NQO to induce respiration‐deficient mutant in Sacharomyces cerevisiae . Kawazoe et al () showed that chlorine, methyl, and methoxy incorporations at position C‐3 of 4‐NQO remove totally the carcinogenicity of this molecule in mice, whereas C‐3 bromine atom and C‐2 methyl incorporations do not.…”

Section: Discussionmentioning

confidence: 99%

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

Duran

Rincón

Galvis

et al. 2013

Environmental Toxicology

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Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

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INDUCTION OF RESPIRATION‐DEFICIENT MUTANT OF SACCHAROMYCES CEREVISIAE BY CARCINOGENIC AGENT, 4‐NITROQUINOLINE N‐OXIDE AND THE EXISTENCE OF TOXOHORMONE‐LIKE FACTOR IN THE MUTANT

Cited by 15 publications

References 17 publications

EFFECT OF METHYLENE BLUE ON THE ACTION OF 4‐NITROQUINOLINE N‐OXIDE AND ACRIFLAVINE IN INDUCING RESPIRATION‐DEFICIENT MUTANTS OF SACCHAROMYCES CEREVISIAE

EFFECT OF METHYLENE BLUE ON THE ACTION OF 4‐NITROQUINOLINE N‐OXIDE AND ACRIFLAVINE IN INDUCING RESPIRATION‐DEFICIENT MUTANTS OF SACCHAROMYCES CEREVISIAE

Preferential alkylation of mitochondrial deoxyribonucleic acid by N-methyl-N-nitrosourea

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

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