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,

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Genetic population structure of Atlantic and Mediterranean albacore Thunnus alalunga was investigated using nucleotide sequence variations of the glucose-6-phosphate dehydrogenase gene intron (G6PD) and the mitochondrial DNA (mtDNA) D-loop region (Dloop). Restriction analysis using Ase I digestion detected two major restriction types (A and B) at the Dloop locus with strong frequency differences between Atlantic and Mediterranean samples. Thirty-six individuals of 100 Mediterranean albacore were of the B type whereas no B type individuals were found in the Atlantic samples (n=102). Phylogenetic analysis using nucleotide sequence data of the Dloop locus indicated that the B type lineage recently arose from the ancestral A lineage in the Mediterranean Sea and has not dispersed into the Atlantic Ocean. The frequencies of two alleles (L and S) at the G6PD locus were significantly different between the samples from the Atlantic (L=0.495) and the Mediterranean (L=0.725), but no significant heterogeneity was observed between mtDNA-A and -B types of the Mediterranean sample. These molecular data indicate that gene flow between the Atlantic and Mediterranean albacore populations have been considerably restricted and strongly suggest these populations should continue to be treated as two distinct management units