Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Genetic instability of human cells with DNA related to human retrovirus (Meeting abstract).
International Association for Comparative Research on Leukemia and Related Diseases, 16th Symposium. July 11-16, 1993, Montreal, Quebec, Canada, A56, 1993.. Unique Identifier : AIDSLINE ICDB/94698654 Maruyama K; Fukushima T; Mochizuki S; Kawamura K; Koshikawa N; Miyauchi M; Nakano M; Chiba Cancer Center Res. Inst., Chiba, Japan
Abstract:
Our earlier observation of the higher HTLV-I seroprevalence in nontransfused cancer patients than in healthy persons prompted us to search for DNA sequences related to HTLV-I in cancer patients. DNA was extracted from paraffin-embedded tissues, sera, and/or cultured cells from 20 HTLV-I seropositive patients including those with hematologic and with nonhematologic malignancies. Extracted DNA was subjected to PCR and analyzed in PAGE or SSCP by Southern hybridization for HTLV-I and/or HTLV-II-related DNA. LTR, gag, and/or tax-related sequences were detected in PBL, lymph nodes, and tumor tissues including carcinomas of the uterus, prostate, and urinary bladder. In cultured fibroblasts, these sequences showed mobilities different from those in lymphoid cells of the same patients. By in situ hybridization, these sequences were detected in tumor cells and lymphoid cells. They were undetectable in most, but not all, non-neoplastic tissues of HTLV-I seronegative patients examined. To investigate a possible relevance of these sequences to the neoplastic change of host cells, normal human lymphocytes were infected in vitro with HTLV-I and examined for changes in their growth potential, chromosomes, and in gene product expression. Following virus infection, they achieved continuous growth in conditioned culture media, showed specific chromosome abnormalities, and changes in viral and cellular gene product expression. Exposure of these cells to MNNG or to ultraviolet rays resulted in transformation and in additional changes of particular chromosomes showing similar G-band abnormalities among those seen in different transformed cell lines. Altered expression of the product of cellular genes including c-jun and c-fos known to be carried by chromosomes with detected G-band abnormalities was observed by immunostaining with relevant monoclonal antibodies. These results suggest that DNA related to human retrovirus may be present in different tissues of some individuals, and that these sequences may cause genetic instability of host cells rendering them susceptible to carcinogenesis.
Keywords: Carcinogens/PHARMACOLOGY Cell Transformation, Neoplastic/DRUG EFFECTS/RADIATION EFFECTS Chromosome Abnormalities DNA, Viral/*ANALYSIS Gene Expression Gene Products, tax/GENETICS Genes, gag Human HIV Seroprevalence HTLV-I/*GENETICS HTLV-I Infections/EPIDEMIOLOGY Lymphoid Tissue/PATHOLOGY Neoplasms/GENETICS Repetitive Sequences, Nucleic Acid ABSTRACT 940830
M9480796
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