Clastogenic effects of different Ureaplasma urealyticum serovars on human chromosomes.

The possibility that Ureaplasma urealyticum might play an important role in human infertility was first raised more than 20 years ago, but this association remains speculative. Considering the hypothesis that the pathogenicity of Ureaplasma urealyticum may depend on its serotypes, the clastogenic effects of different strains of Ureaplasma urealyticum, at concentrations of 10(3) CCU (color changing units)/ml, 10(4) CCU/ml and 10(5) CCU/ml, were evaluated in vitro in short-term cultures of human lymphocytes. Total or partial mitotic inhibition was produced by Ureaplasma urealyticum serotypes 2, 3 and 10 independent of the concentration (10(3) CCU/ml, 10(4) CCU/ml or 10(5) CCU/ml) of the microorganisms employed. In contrast, the clastogenic effects observed with serotypes 1, 7 and 12 varied according to the concentration employed in the test. Mitotic alterations were observed in Ureaplasma urealyticum serotypes 5, 6, 7, 8, 9, 11 and 12. Chromatid gaps (53.0%) and chromatid breaks (13.9%) were the most frequent types of alterations observed. The results of this in vitro assay demonstrated that the clastogenic effects varied with the Ureaplasma urealyticum serotypes evaluated.

Chromosome studies in HTLV-I, -II, and HIV-1, -2 cell lines infected in vivo and in vitro.

HTLV-I, II and HIV-1, 2 are T-cell tropic viruses, all belonging to the retrovirus family. These viruses are transmitted horizontally by intimate contact or through blood products. The study of chromosomal changes in these T cells may enhance our understanding of the nature and mechanism of these viral infections. However, because of the cytopathic effect of these viruses on T cells, the direct observation of abnormalities in these cells is sometimes difficult. We performed chromosomal analysis on six HTLV-I cell lines from patients with HTLV-I-positive leukemia/lymphoma, one HTLV-I variant cell line, and two HTLV-II-positive cell lines. The results of these studies were compared with the findings in an earlier (published) study of direct preparations and short-term cultures of cells from 11 HTLV-I-positive NIH patients. Our study also included cytogenetic analysis of seven established cell lines and six normal peripheral bloods infected in vitro with the HTLV-IIIB strain of HIV-1 (five cell lines and six bloods) or HIV-2 (two lines); all were studied both before and after viral infection. The results showed that all six HTLV-I cell lines and the variant cell line had multiple chromosomal changes: three lines had deletions of chromosome 6, with breakpoints between q21 and q25. Nine of the 11 NIH patients with HTLV-I had clonal abnormalities, and six of these nine had chromosome 6 deletions with breakpoints ranging from band q11 to band q23. The high incidence of 6q involvement may be of considerable significance in this clinical subgroup of HTLV-I patients. The two HTLV-II cell lines were established from patients suffering from HTLV-II infection. Both of these cell lines had translocations of chromosome 21 at p11, and both had extra copies of chromosome 20; no known oncogenes or receptors are located on these two chromosomes. Chromosome 17 was the chromosome most frequently involved (three lines) in the five HIV-1-infected cell lines, followed by chromosomes 3 and 21; it is of interest that NGL (also known as C-ERBB2 or NEU oncogene), CD7 (a lymphocyte antigen), HTLV-1 receptor, NGFR (nerve growth factor receptor), and MIC6 are all cell surface antigens coded by genes on chromosome 17q. No specific chromosome abnormalities were found in the normal blood samples infected with HIV-1, and no unique chromosome changes were noted in the two cell lines infected with HIV-2; however, the infected H9 line had a chromosome 17 abnormality, a translocation involving band 17p11.

Oncogenes in retroviruses, malignancy, and normal tissues.

Oncogenes are genes with a proven cancer association that appear to function primarily in the regulation of cellular proliferation and differentiation. The preliminary work leading to their discovery, their association with retroviruses, the retrovirus life cycle, and the use of retroviruses to find and characterize oncogenes is discussed in detail. Chromosomal abnormalities are discussed using Burkitt's lymphoma and the myc oncogene as prototypes. Finally, the normal (nonmalignant) functioning of oncogenes is discussed in terms of embryogenesis and hepatic regeneration.

Venezuelan encephalitis virus: in vivo induction of a chromosomal abnormality in hamster bone marrow cells.

This study reports the induction in vivo of aneuploidy in bone marrow cells of the Syrian hamster after short-term infection with Venezuelan encephalitis virus.

Elevated expression of T-antigen in simian papovavirus 40-infected skin fibroblasts from individuals with cytogenetic defects.

A number of cytogenetic conditions were examined for expression of simian papovavirus 40 T-antigen in vitro. Skin fibroblasts from patients with Turner's syndrome and trisomy 18 syndrome and most cell lines from Klinefelter's syndrome, trisomy 13 syndrome, chromosomal translocations, chromosome 21 deletions, and single cases of 18q- and 4p- exhibited elevated T-antigen expression, compared to a clinically and cytogenetically normal control population. Thus, T-antigen expression was generally elevated in cells with increased, decreased, or rearranged genetic material involving many different chromosomes. Variation in T-antigen expression among cell lines may reflect two factors. Individual cell line factors may account for differences within homogeneous clinical groups, whereas population factors appear to account for differences between the various clinical groups and the control population. The observation of elevated T-antigen expression in diverse cytogenetic conditions suggests that this phenomenon may be a manifestation of chromosomal aberration unrelated to cancer susceptibility.