Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats.
Rat lymphoid cells, TARS-1, immortalized by coculture with adult T-cell leukemia cells, were intraperitoneally injected into 65 newborn, inbred WKAH/Hkm rats. In most of the rats, tumor nodules were discernible 7 to 15 days after transplantation but were completely rejected within 5 to 6 weeks. Two rats with no tumor nodules exhibited gait disturbances and paralysis of the hind legs 3 to 4 weeks after transplantation. Histological and hematological examinations revealed that a lymphoma/leukemia-like disease had developed in one of the two rats, and the T-lymphoid cell line WLeuk-1 was established from peripheral blood mononuclear cells from this rat. When the WLeuk-1 cells were transplanted into newborn WKAH/Hkm rats, the animals died of a lymphoma/leukemia-like disease within several weeks after transplantation, in contrast to their rejection of the TARS-1 cells. Southern blot and karyotype analyses revealed that WLeuk-1 cells had retained the marker chromosomes and human T-lymphotropic virus type I (HTLV-I) integration patterns of the parent cell line, TARS-1. The additional specific chromosome abnormalities 3p+,t (12;13), and Xq+ were found in the WLeuk-1 cells. Moreover, the expression of HTLV-I structural proteins was slightly depressed in WLeuk-1 cells, while that of the transacting factors p40tax and p21x, but not that of p27rex, was enhanced about fivefold compared with that in TARS-1. The transactivating function of p40tax was intact in WLeuk-1, as evidenced by enhanced interleukin-2 receptor alpha chain expression. These results suggest that aberrant expression of HTLV-I regulatory genes and alteration of cellular genes were associated with the phenotypic progression of the WLeuk-1 cell line.
Oka
T
T
Department of Pathology, Kochi Medical School, Japan.
Sonobe
H
H
Iwata
J
J
Kubonishi
I
I
Satoh
H
H
Takata
M
M
Tanaka
Y
Y
Tateno
M
M
Tozawa
H
H
Mori
S
S
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D015490:HTLV-I Infections / Q000382:microbiology* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007621:Karyotyping; D015458:Leukemia, T-Cell / Q000382:microbiology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000382:microbiology* / Q000473:pathology / Q000637:transplantation; D008223:Lymphoma / Q000382:microbiology* / Q000473:pathology; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains