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Titolo:
MUTAGENICITY AND CYTOTOXICITY OF REACTIVE OXYGEN AND NITROGEN SPECIESIN THE MN-11 MURINE TUMOR-CELL LINE
Autore:
SANDHU JK; BIRNBOIM HC;
Indirizzi:
UNIV OTTAWA,DEPT IMMUNOL & MICROBIOL,501 SMYTH RD OTTAWA ON K1H 8L6 CANADA UNIV OTTAWA,DEPT IMMUNOL & MICROBIOL OTTAWA ON K1H 8L6 CANADA OTTAWA REG CANC CTR OTTAWA ON K1H 8L6 CANADA
Titolo Testata:
Mutation research
fascicolo: 2, volume: 379, anno: 1997,
pagine: 241 - 252
SICI:
0027-5107(1997)379:2<241:MACORO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHINESE-HAMSTER CELLS; MOUSE-LYMPHOMA-CELLS; NITRIC-OXIDE; MAMMALIAN-CELLS; GLYCERYL TRINITRATE; HYDROGEN-PEROXIDE; DNA-DAMAGE; SALMONELLA-TYPHIMURIUM; MUTATION-INDUCTION; MOLECULAR ANALYSIS;
Keywords:
NITRIC OXIDE; MUTAGENICITY; MUTANT FREQUENCY; REACTIVE OXYGEN SPECIES; REACTIVE NITROGEN SPECIES; GLYCERYL TRINITRATE; SODIUM NITROPRUSSIDE; NO-DONATING DRUGS; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE (HPRT) GENE; MOUSE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
51
Recensione:
Indirizzi per estratti:
Citazione:
J.K. Sandhu e H.C. Birnboim, "MUTAGENICITY AND CYTOTOXICITY OF REACTIVE OXYGEN AND NITROGEN SPECIESIN THE MN-11 MURINE TUMOR-CELL LINE", Mutation research, 379(2), 1997, pp. 241-252

Abstract

There is increasing evidence that endogenously generated reactive oxygen (ROS) and reactive nitrogen (RNS) species at sites of inflammationand in tumors may be genotoxic. We have developed a murine tumor model (MN-11) in which mutations at the hypoxanthine phosphoribosyltransferase (HPRT) locus, arising both in vitro and in vivo, can be detected. In the present report, we describe an in vitro study of the ability of ROS and RNS to induce mutations in our model system. Cs-137 radiation and radiomimetic drugs caused a dose-dependent increase in mutant frequency. At D-0, radiation induced about 170 mutants per 10(5) viable cells, compared to 50 and 95 for streptonigrin and bleomycin, respectively. H2O2 induced a lower frequency of mutants, 20-30 per 10(5) for enzymatically generated or bolus, respectively. For the following treatments, mutant frequency at 50% survival is shown. Incubation with human granulocytes induced a low frequency of mutants (about 15 per 10(5)). RNS was tested using a series of NO-donating drugs. Spermine/NO . induced cytotoxicity but no mutants while S-nitroso-N-acetylpenicillamine induced a low level, 10 per 10 Both release nitrogen monoxide spontaneously, with a t(1/2) < 3 h. Glyceryl trinitrate and sodium nitroprusside are two drugs that were slowly metabolized by MN-11 cells (> 12 h). Glyceryl trinitrate induced about 20 per 10(5) while nitroprusside induced 50 per 10(5). Our results indicate that RNS can readily inducemutations detectable in MN-11 cells. At equicytotoxic doses, the induced mutant frequency varied considerably for different drugs, suggesting that different states of nitrogen monoxide (such as NO+ or NO .) may be generated and these may vary in their mutagenic/cytotoxic potential. (C) 1997 Elsevier Science B.V.

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Documento generato il 25/11/20 alle ore 09:59:26