Cytogenetic analysis of spontaneous and 2-cyanoethylene oxide-induced tk-/- mutants in TK6 human lymphoblastoid cultures.
Two phenotypic classes of selectable tk-/- mutants have been isolated from the TK6 human lymphoblast cell line; one has a normal growth rate (tkn) relative to the parental cell line; the other has a slow growth rate (tks). Complete karyotypes of metaphase chromosomes were prepared and analyzed from 16 tks mutants (eight spontaneous and eight 2-cyanoethylene oxide [CNEtO]-induced), two spontaneous tkn mutants, and the parental TK6 cell line. Southern blot analysis of these tk-/- mutants indicated that all had lost a 14.8 kb polymorphic band corresponding to the active tk allele. No chromosome abnormalities with respect to the parental cell line TK6 were observed in eight spontaneous tks mutants. Chromosome abnormalities that may have been related to CNEtO treatment were observed in four of eight CNEtO mutants. However, chromosome 17, containing the tk locus in man, was cytologically normal with respect to the parental TK6 cell line in 15 of 16 tks mutants. A visible abnormality of chromosome 17 was present in one CNEtO-induced tks mutant. The abnormality was a duplication of the long arm of the chromosome 17, with break points at q11 and q21. The latter break point is close to the site of the tk locus, suggesting that the aberration observed may be associated with tk-/- phenotype. These observations contrast with the relatively high incidence (greater than or equal to 59%) of chromosome 11 abnormalities reported in tks (small colony) mouse lymphoma L5178Y/TK +/- mutants.
Kodama
Y
Y
Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Boreiko
C J
CJ
Skopek
T R
TR
Recio
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L
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002869:Chromosome Aberrations; D005027:Ethylene Oxide / Q000633:toxicity / Q000031:analogs & derivatives; D006801:Humans; D007621:Karyotyping; D009154:Mutation; D010641:Phenotype; D013937:Thymidine Kinase / Q000235:genetics*
C033154:2-cyanoethylene oxide; D013937:Thymidine Kinase; D005027:Ethylene Oxide