Identification of the Adenovirus Type 12 Gene Product(s) Required for Induction of Chromosomal Aberrations in Human Cells

Abstract

Unlike most RNA and DNA containing viruses, which induce cytogenetic damage at random sites throughout the human genome, the highly oncogenic adenovirus type 12 is also capable of inducing damage at specific chromosomal sites. Infection of human embryonic retinal or kidney cells with Ad12 results in the induction of heterochromatic gaps at specific (17q21-22, 1p36, 1q21, and 1q42-43) and random sites in the cellular chromosome. Previous work by Durnam et al. (1986) demonstrated that the viral early region 1 (E1) is sufficient for the induction of damage at band 17q21-22. The objective of the present study was to 1) identify the Ad12 E1 gene product(s) required for the induction of aberrations in human diploid cells, and 2) to determine whether the same or different functions are involved in the induction of damage at specific and random sites. To this end, adenovirus type 12/adenovirus type 5 recombinants with hybrid E1 sequences as well as viruses with mutations in the Ad12 E1B genes were used to map the Ad12 E1 function(s) required for the induction of chromosomal aberrations. The results of this study indicate that the expression of E1A proteins is not sufficient for this effect. On the other hand, mutations within the E1B 55Kd protein but not the E1B 19Kd protein were found to affect the ability of the virus to induce both specific and random damage (Schramayr et al., 1990).