Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Induction of single-strand DNA breaks in cells infected with the human T-cell leukemia virus or bovine leukemia virus (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 35:A3392 1994. Unique Identifier : AIDSLINE ICDB/95605077 Philpott SM; Buehring GC; School of Public Health, Univ. of California at Berkeley,; Berkeley, CA 94720
Abstract:
Majone et al (Virology 193:456, 1993) recently demonstrated that human lymphocytes transiently transfected with a plasmid encoding the p40tax oncoprotein of the human T-cell leukemia virus (HTLV) are twice as likely to exhibit de novo formation of micronuclei than mock transfected cells. Experiments in our laboratory have since confirmed these results, demonstrating that cells infected with HTLV-1, HTLV-2, and the closely related bovine leukemia virus (BLV) all demonstrate increased rates of micronuclei formation (Philpott and Buehring, unpublished data). These micronuclei are small nuclear bodies which result from chromosomal damage; they contain either chromosomal fragments or entire chromosomes that have failed to attach to the mitotic spindle during cell division. It could thus be suggested that HTLV p40tax and BLV p38tax oncoproteins induce cellular transformation by either inducing DNA damage or by inhibiting cellular repair of spontaneously induced damage. To test this theory, we used a fluorescence assay which detects the relative frequency of DNA breaks to examine the effects of HTLV or BLV infection on the integrity of host-cell DNA. To date 23 different cell lines have been examined; the cell lines tested were known to be either virally uninfected, or infected with various oncogenic RNA or DNA viruses. Our preliminary results suggest infection of cells with HTLV and BLV leads to a significant increase in the number of single-stranded breaks in the host-cell DNA; these changes appeared to be stable over time. These data support the general hypothesis that HTLV- and BLV-induced cellular transformation is related to DNA damage.
Keywords: Animal Cattle Cell Line Cell Transformation, Neoplastic/*GENETICS Cell Transformation, Viral/*GENETICS DNA Damage/*GENETICS DNA Repair/GENETICS Human HTLV-BLV Viruses/*GENETICS Leukemia Virus, Bovine/*GENETICS Micronucleus Tests ABSTRACT 950430
M9541149
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