Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
MUTAGENICITY AND CYTOTOXICITY OF NAPHTHOQUINONES FOR AMES SALMONELLA TESTER STRAINS
Autore:
HAKURA A; MOCHIDA H; TSUTSUI Y; YAMATSU K;
Indirizzi:
EISAI & CO LTD,DEPT DRUG SAFETY RES,1-3 TOKODAI,5-CHOME TSUKUBA IBARAKI 30026 JAPAN
Titolo Testata:
Chemical research in toxicology
fascicolo: 4, volume: 7, anno: 1994,
pagine: 559 - 567
SICI:
0893-228X(1994)7:4<559:MACONF>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
BIOREDUCTIVE ALKYLATING-AGENTS; ANTI-CANCER AGENTS; DT-DIAPHORASE; PARA-BENZOQUINONE; ISOLATED HEPATOCYTES; FREE-RADICALS; DNA ADDUCTS; HL-60 CELLS; QUINONES; GLUTATHIONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
A. Hakura et al., "MUTAGENICITY AND CYTOTOXICITY OF NAPHTHOQUINONES FOR AMES SALMONELLA TESTER STRAINS", Chemical research in toxicology, 7(4), 1994, pp. 559-567

Abstract

The molecular mechanisms involved in quinone cytotoxicity, especiallymutagenicity, are still largely unknown. In order to better understand the molecular aspects of the mechanisms of quinone mutagenicity and cytotoxicity, we examined them by using a series of 13 simple structural naphthoquinone (NQ) derivatives for 9 Ames Salmonella mutagenicity tester strains in the presence or absence of liver homogenate S9 mix from rats induced with phenobarbital and 5,6-benzoflavone. Most NQs used in this study showed mutagenicity with and/or without S9 mix. The most potent mutagenic NQ was 2,3-dichloro-1,4-NQ, with mutagenicity of 18 induced revertants/nmol/plate for strain TA104 without S9 mix. Amongthe strains used, TA104, which is sensitive to oxidative mutagens, was the most sensitive to the NQs, and the second most sensitive strain was TA2637, which detects bulky DNA adducts. The relationship of mutagenic potency to the one-electron reduction potential with TA104 suggested that the higher redox potential NQs were more mutagenic than the lower redox potential NQs. Significant reduction of the mutagenicity of1,4-naphthoquinone without S9 mix was observed in the presence of catalase. Enhancement of the mutagenic potential of the NQs by the pKM101plasmid implicated in error-prone repair was also observed. The most cytotoxic NQ was 2,3-dichloro-5,8-dihydroxy-1,4-NQ, and the least cytotoxic NQ was beta-NQ-4-sulfonic acid potassium salt, a 700-fold range in potency. The cytotoxic effect of the NQs was largely dependent on the structures of their substituents. It was suggested that the higher redox potential NQs were more cytotoxic than the lower redox potentialNQs for all of the strains used, in contrast to the mutagenicity of the NQs. The presence of S9 mix decreased the cytotoxic effect of the NQs, the extent of which was also largely dependent on the structures of their substituents and is in accordance with the order of the heightof the one-electron reduction potentials. These results indicate thatthe mutagenicity of NQs in Salmonella typhimurium was due to oxidative damage produced with activated oxygen species such as hydroxy radical and superoxide anion radical, which are generated as a result of thereduction of the NQs, and to bulky NQ-DNA adducts accounting for their electrophilic property, whose contribution was largely dependent on the substituents of NQs. On the other hand, it was suggested that cytotoxicity of NQs for S. typhimurium was mainly derived from oxidative damage.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 07:57:02