Reverse Transcriptase: A Molecular Probe for the Expression of Retroviral Information in Human Tumors

Abstract

The discovery of reverse transcriptase in RNA tumor viruses (Temin and Mizutani, 1970; Baltimore, 1970), implicated by the provirus hypothesis of Temin (Temin, 1964a, 1964b), was a new dimension in the understanding of how such viruses multiply and moreover, how do they catalyze neoplastic transformation. Soon after the discovery of reverse transcriptase in retroviruses, Gallo and his associates detected a similar enzymic activity in lymphoblasts of patients with leukemia (Gallo et al., 1970). This activity was absent in mitotically stimulated normal human peripheral blood leucocytes. The first detection of intracellular reverse transcriptase in leukemic cells (Gallo et al., 1970) provided incentive to examine this activity in other human tumor tissues (Chandra, 1979; Chandra and Steel, 1977, 1980; Chandra et al., 1975, 1978, 1980, 1981; Ebener et al., 1979? Ohno et al., 1977; Poiesz et al., 1980; Welte et al., 1979; and Witkin et al., 1975). The main objective of these studies was: 1) to understand whether this is a new enzyme or is simply a modified form of one of the constitutive cellular DNA polymerases α, β and γ, 2) to develop new procedures of purifying this viral-like reverse transcriptase from neoplastic tissues, and 3) to characterize the purified reverse transcriptase from human tumor tissues to determine whether the detection of this enzyme indicates an expression of retrovirus information in these tissues.