Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats

Takashi Oka, Hiroshi Sonobe, Jun Iwata, Ichiro Kubonishi, Hitoshi Satoh, Masaru Takata, Yuetsu Tanaka, Masatoshi Tateno, Hideki Tozawa, Shigeo Mori, Takashi Yoshiki, Yuji Ohtsuki

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Abstract

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 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.

Original languageEnglish
Pages (from-to)6686-6694
Number of pages9
JournalJournal of Virology
Volume66
Issue number11
Publication statusPublished - Nov 1992
Externally publishedYes

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lymphoma
leukemia
Lymphoma
Leukemia
cell lines
Lymphocytes
Viruses
Cell Line
viruses
rats
cells
Transplantation
neonates
Interleukin-2 Receptor alpha Subunit
Virus Integration
Viral Structural Proteins
Adult T Cell Leukemia Lymphoma
neoplasms
chromosome aberrations
Paraplegia

ASJC Scopus subject areas

  • Immunology

Cite this

Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats. / Oka, Takashi; Sonobe, Hiroshi; Iwata, Jun; Kubonishi, Ichiro; Satoh, Hitoshi; Takata, Masaru; Tanaka, Yuetsu; Tateno, Masatoshi; Tozawa, Hideki; Mori, Shigeo; Yoshiki, Takashi; Ohtsuki, Yuji.

In: Journal of Virology, Vol. 66, No. 11, 11.1992, p. 6686-6694.

Research output: Contribution to journalArticle

Oka, T, Sonobe, H, Iwata, J, Kubonishi, I, Satoh, H, Takata, M, Tanaka, Y, Tateno, M, Tozawa, H, Mori, S, Yoshiki, T & Ohtsuki, Y 1992, 'Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats', Journal of Virology, vol. 66, no. 11, pp. 6686-6694.
Oka, Takashi ; Sonobe, Hiroshi ; Iwata, Jun ; Kubonishi, Ichiro ; Satoh, Hitoshi ; Takata, Masaru ; Tanaka, Yuetsu ; Tateno, Masatoshi ; Tozawa, Hideki ; Mori, Shigeo ; Yoshiki, Takashi ; Ohtsuki, Yuji. / Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats. In: Journal of Virology. 1992 ; Vol. 66, No. 11. pp. 6686-6694.
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abstract = "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 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.",
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AU - Yoshiki, Takashi

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