Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells II. Test validation and interpretation

Amacher, David E.; Paillet, Simone C.; Turner, Gail N.; Ray, Verne A.; Salsburg, David S.

doi:10.1016/0027-5107(80)90118-9

Cited by 127 publications

(14 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, a review of the MLA database at LRL supports the findings of Amacher et al [1980] and suggests that toxicity is one parameter contributing to the high incidence of unique positive results in the MLA. Moreover, a group working with the Safety Expert Working Group of the International Conference on Harmonisation of Genetic Toxicology Testing Procedures has recently proposed standards for the MLA [Clive et al, 19951. In the report, the group cautioned the experimenter about biologically irrelevant effects that might occur in severely stressed cells.…”

Section: Resultssupporting

confidence: 63%

“…Krehl and Clive [1989] reevaluated 12 compounds in the MLA that were initially reported positive in the NTP and downgraded 5 of the chemicals to negative, marginal, equivocal, or nontestable. While a 10-20% RTG appears to be an acceptable lower level, Amacher et al [1980] suggested that RTG be limited to 20%, as a higher number of positives was obtained with nonmutagens in their laboratory when RTG values fell below 20%. Li et al [1991] also suggested that more stringent requirements for positive results should be considered.…”

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Influence of cytotoxicity on test results in the L5178Y TK+/− mouse lymphoma assay

Oberly

Garriott

1996

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 63%

Section: Introductionmentioning

confidence: 93%

Influence of cytotoxicity on test results in the L5178Y TK+/− mouse lymphoma assay

Oberly

Garriott

1996

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

“…A number of investigators have monitored trifluorothymidine (TFT) resi.stance in L5178Y mouse cells to identify the mutagenic activity of chemieals (Cl ive et al , 1972;Amacher et al , 1980;Oberly etal., 1984;Caspary and Myhr, 1986;McGregoretal., 1989McGregoretal., , 1991Myhr et al, 1990;Stopper et al, 1993b). The L5178Y mouse cell line, clone 3.7.2c, is heterozygous at the thymidine kinase (tk) locus.…”

Section: Introductionmentioning

confidence: 99%

Is micronucleus induction by aneugens an early event leading to mutagenesis?

Stopper¹,

Eckert²,

Schiffmann³

et al. 1994

Mutagenesis

View full text Add to dashboard Cite

“…The L5178Y/TK+/-mouse lymphoma assay was conducted using modifications of the procedures described by Clive et al, 1979 andAmacher et al, 1980. Cells were maintained in RPMI-1640 medium supplemented with 1.0 mM sodium pyruvate, 0.5% pluronic F68, 50 units/ml penicillin and 50 /~g/ml streptomycin, hereafter referred to as RoP.…”

Section: Methodsmentioning

confidence: 99%

Genetic toxicity evaluation of McN-5195: A novel analgesic

et al. 1988

View full text Add to dashboard Cite

McN-5195, (+/-)-trans-3-(2-bromophenyl)octahydroindolizine, a novel analgesic, was tested for genotoxic potential in a battery of tests with endpoints of mutagenicity, chromosomal alterations and DNA damage/repair. McN-5195 was not mutagenic when tested in the Ames test using strains TA98, TA100, TA1535, TA1537 and TA1538, in the absence of metabolic activation and in the presence of Aroclor 1254-induced rat or hamster S-9. Negative results were also obtained in the mouse lymphoma assay in the absence of activation, but reproducible mutagenic responses were seen in this mammalian cell assay in the presence of rat S-9 at high levels of induced toxicity (reduced cell growth). Testing of the enantiomers of McN-5195 in this assay supported these findings. A predominance of small mutant colonies in the mouse lymphoma assay suggested a potential chromosomal effect of McN-5195. This was confirmed with positive findings in an in vitro cytogenetics assay using CHO cells, again at toxic exposure levels and only in the presence of S-9. McN-5195 did not induce DNA repair in the primary rat hepatocyte/DNA repair assay, nor did it induce alterations in vivo of chromosome structure or number when tested in a rat bone marrow cytogenetics assay. The findings from this battery of tests indicate that McN-5195 has modest genotoxic activity when tested in the presence of rat liver S-9 in in vitro systems sensitive to cytogenetic change. The absence of genotoxicity in vitro in Salmonella and intact liver cells and in vivo in rat bone marrow suggests that McN-5195 is unlikely to present a genotoxic risk to whole animals.

show abstract

Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells II. Test validation and interpretation

Cited by 127 publications

References 15 publications

Influence of cytotoxicity on test results in the L5178Y TK+/− mouse lymphoma assay

Influence of cytotoxicity on test results in the L5178Y TK+/− mouse lymphoma assay

Is micronucleus induction by aneugens an early event leading to mutagenesis?

Genetic toxicity evaluation of McN-5195: A novel analgesic

Contact Info

Product

Resources

About