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Titolo:
MOLECULAR ANALYSIS OF LACI MUTATIONS IN RAT2(TM) CELLS EXPOSED TO 7,12-DIMETHYLBENZ[A]ANTHRACENE - EVIDENCE FOR DNA-SEQUENCE AND DNA STRANDBIASES FOR MUTATION
Autore:
MANJANATHA MG; CHEN JB; SHADDOCK JG; HARRIS AJ; SHELTON SD; CASCIANO DA;
Indirizzi:
NATL CTR TOXICOL RES,DIV GENET TOXICOL,FOOD & DRUG ADM,DEPT HLTH & HUMAN SERV JEFFERSON AR 72079
Titolo Testata:
Mutation research
fascicolo: 1, volume: 372, anno: 1996,
pagine: 53 - 64
SICI:
0027-5107(1996)372:1<53:MAOLMI>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAMSTER OVARY CELLS; UV-INDUCED MUTATIONS; TRANSGENIC MICE; EXCISION-REPAIR; HPRT GENE; HA-RAS; MAMMARY CARCINOGENESIS; TRANSCRIBED STRAND; HUMAN FIBROBLASTS; SHUTTLE VECTOR;
Keywords:
LACI; RAT2(TM) CELL; MUTANT FREQUENCY; STRAND BIAS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
M.G. Manjanatha et al., "MOLECULAR ANALYSIS OF LACI MUTATIONS IN RAT2(TM) CELLS EXPOSED TO 7,12-DIMETHYLBENZ[A]ANTHRACENE - EVIDENCE FOR DNA-SEQUENCE AND DNA STRANDBIASES FOR MUTATION", Mutation research, 372(1), 1996, pp. 53-64

Abstract

The Rat2(TM) cell line carries 50-70 stably integrated copies per cell of a lambda/lacl shuttle vector asa target for mutagenicity testing. Rat2(TM) cells were exposed to 1 and 10 mu g/ml of 7,12-dimethylbenz[a]anthracene (DMBA) for 24 h at 37 degrees C in the presence of primary rat hepatocytes, and grown to confluence. The shuttle vector was rescued from untreated and mutagen-treated cells and mutant frequencies were determined. The low and high doses of DMBA induced mutant frequencies that were 7-fold (25 +/- 4.9 x 10(-5)) and 33-fold (127 +/- 19.9 x10(-5)) higher, respectively, than the spontaneous mutant frequency (3.8 +/- 0.7 x 10(-5)). DNA sequence analysis of the DMBA-induced lacl(-) mutants indicated that they contained mainly basepair substitution mutations at A:T and G:C, and that A:T --> T:A and G:C --> T:A transversions were the predominant types. In addition, 23 of 28 (82%) A:T basepair substitution mutations occurred with the mutated dA, the putatively adducted base, on the coding strand. Furthermore, 20 of the 28 (71%) A:T mutations had the mutated dA flanked 5' by a dC, and 17 of these were A:T --> T:A transversions, suggesting a sequence preference forthis mutation. Except for a higher proportion of G:C --> A:T transitions in the low dose data, the mutational profiles from low and high doses of DMBA were similar. These results indicate that DMBA mutagenesisin the lacl gene of Rat2(TM) cells displays distinct DNA sequence andDNA strand preferences.

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Documento generato il 01/04/20 alle ore 23:21:24