Consensus agreement regarding protocol issues discussed during the mouse lymphoma workshop: Portland, Oregon, may 7, 1994

Clive, D.; Bölcsföldi, George; Clements, Julie; Cole, Jane; Homna, Masamitsu; Majeska, Jenness B.; Moore, Martha M.; Müller, Lutz; Myhr, B.; Oberly, T.J.; Oudelhkim, Marie-Claude; Rudd, Colette J.; Shimada, Hiroyasu; Sofuni, Toshio; Thybaud, Véronique; Wilcox, Philip

doi:10.1002/em.2850250211

Cited by 44 publications

(38 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To demonstrate acceptable cell growth and maintenance throughout the experiment, the absolute plating efficiency for solvent control should be 60-140% for survival (PE 0 ) and 70-130% for viability (PE 2 ) according to the 1994 consensus agreement formed by the MLA workshop at Portland, OR (Clive et al, 1995). In the present studies, however, we accepted absolute plating efficiencies that were slightly outside these ranges.…”

Section: Criteria Of Acceptable Conditionsmentioning

confidence: 96%

“…According to the Portland agreement (Clive et al, 1995), the top concentration should show 10-20% RS or RTG, whichever is lower. In the present study, the data obtained under an excessive cytotoxic condition (Ͻ10% RS or RTG) were excluded from the evaluation.…”

Section: Criteria Of Acceptable Conditionsmentioning

confidence: 99%

“…In 88% of the phase 1 and 91% of the phase 2 experiments spontaneous mutation frequencies were within the range 50-250ϫ10 -6 . The 1994 consensus agreed that spontaneous mutation frequencies Ͻ60ϫ10 -6 should be viewed with caution for the microwell method, but no statement was made about an acceptable upper limit (Clive et al, 1995). Mutation frequency of positive control.…”

Section: Comparison Of Experimental Conditions and Data Qualitiesmentioning

confidence: 99%

“…Top concentration. According to the 1994 consensus agreement (Clive et al, 1995), the highest concentration should cause 10-20% RS or RTG. In the 94 phase 1 experiments, 13 experiments on three chemicals (DDC, hexamethyl phosphoramide and urethane) did not show such severe cytotoxicity even at the limit concentration (5 mg/ml).…”

Section: Comparison Of Experimental Conditions and Data Qualitiesmentioning

confidence: 99%

See 3 more Smart Citations

Evaluation of the mouse lymphoma tk assay (microwell method) as an alternative to the in vitro chromosomal aberration test

et al. 1999

View full text Add to dashboard Cite

In order to evaluate the utility of the mouse lymphoma assay (MLA) for detecting in vitro clastogens and spindle poisons and to compare it with the in vitro chromosomal aberration test (CA), we conducted an international collaborative study of the MLA that included 45 Japanese laboratories and seven overseas laboratories under the cooperation of the Ministry of Health and Welfare of Japan and the Japanese Pharmaceutical Manufacturer's Association. We examined 40 chemicals; 33 were reportedly positive in the CA but negative in the bacterial reverse mutation assay, six were negative in both assays and one was positive in both. We assayed mutations of the thymidine kinase (TK) locus (tk) of L5178Y tk ϩ/-mouse lymphoma cells using the microwell method. According to our standard protocol, cells were exposed to the chemical for 3 h, cultured for 2 days and TK-deficient mutants were expressed in 96-well plates under trifluorothymidine. Each chemical was coded and tested by two or three laboratories. Among the 34 CA-positive chemicals, positive MLA results were obtained for 20 and negative results were obtained for nine. The remaining five chemicals were inconclusive or equivocal because of discrepant inter-laboratory results or reproduced discrepant results, respectively. Among the six CA-negative chemicals, one was negative in the MLA, two were positive and three were inconclusive. Thus, the MLA could detect only 59% (20/34) of CA-positive chemicals. We concluded that the MLA was not as sensitive as the CA. Some MLA-negative chemicals evoked positive responses in the CA only after long continuous treatment. These might also be genotoxic in the MLA with long continuous treatment. Improvement of the MLA protocol, including alteration of the duration of the treatment, might render the MLA as sensitive as the CA. IntroductionThe genotoxicity tests that have been developed and validated over the years differ in the biological system used (prokaryotic,

show abstract

Section: Criteria Of Acceptable Conditionsmentioning

confidence: 96%

Section: Criteria Of Acceptable Conditionsmentioning

confidence: 99%

Section: Comparison Of Experimental Conditions and Data Qualitiesmentioning

confidence: 99%

Section: Comparison Of Experimental Conditions and Data Qualitiesmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the mouse lymphoma tk assay (microwell method) as an alternative to the in vitro chromosomal aberration test

et al. 1999

View full text Add to dashboard Cite

show abstract

“…As a positive genotoxic control, TK6 cells were treated with ethyl methanesulphonate (EMS; 5 µg/ml). To measure the spontaneous mutant frequency at each locus, oligonucleotide transfection mixtures were replaced with culture (Clive et al, 1995, Clements, 2000. On the third day, TK6 cells were plated at 1.6 cells per well in 96 well plates to determine cloning efficiency and 20,000 cells per well in trifluorothymidine to determine the TK mutant frequency.…”

Section: Induction Of Rad51 Protein Expression In Tk6 Cells Using Metmentioning

confidence: 99%

Mutagenesis by an Antisense Oligonucleotide and Its Degradation Product

Reshat

Priestley

Gooderham

2012

Toxicological Sciences

View full text Add to dashboard Cite

The European Medicines Agency (EMA) has expressed concern regarding (i) the potential for antisense oligonucleotide (ASO) therapeutics to induce sequence specific mutation at genomic DNA and (ii) the capability of ASO degradation products (nucleotide analogues) to incorporate into newly synthesised genomic DNA via DNA polymerase and cause mutation if base-pairing occurs with reduced fidelity. Treating human lymphoblastoid cells with a biologically active antisense molecule induced sequence specific mutation within genomic DNA over four fold, in a system where RAD51 protein expression was induced. This finding has implications for ASO therapeutics with individuals with an induced DNA damage response, such as cancer patients. Furthermore, a phosphorothioate nucleotide analogue potently induced mutation at genomic DNA two orders of magnitude above control. This study shows that a biologically active ASO molecule can induce heritable sequence alterations, and if degraded, its respective analogue may incorporate into genomic DNA with mutagenic consequences.

show abstract

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

Consensus agreement regarding protocol issues discussed during the mouse lymphoma workshop: Portland, Oregon, may 7, 1994

Cited by 44 publications

References 5 publications

Evaluation of the mouse lymphoma tk assay (microwell method) as an alternative to the in vitro chromosomal aberration test

Evaluation of the mouse lymphoma tk assay (microwell method) as an alternative to the in vitro chromosomal aberration test

Mutagenesis by an Antisense Oligonucleotide and Its Degradation Product

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

Contact Info

Product

Resources

About