Biochemical properties and replication of murine intracisternal a particles during early embryogenesis.

STRINGNER S. YANG,'~ PATRICIA G. CALARCO + and NELSON A. WIVEL~" "~Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014, U.S.A. +Department of Anatomy, University of California, School of Medicine, San Francisco, California 94143, U.S.A. Abstract Intracisternal A particles exhibit features which are characteristic of oncogenic RNA viruses and features which are reminiscent o f fetal antigen expression. Evidence has been developed by ultrastructural study which points toward a vertical transmission of these particles, a situation analogous to known RNA tumor viruses. Intracisternal A particles are readily found in certain preimplantation mouse embryos; they are found occasionally in a variety of neoplasms. Biochemical properties of highly purified intracisternal A particles isolated from murine neuroblastoma cells or plasma cell tumor include high molecular weight 60-70S RNA and an RNA-dependent D NA polymerase. The enzymatic characterization of the A particle DNA polymerase is reported. The enzyme is found analogous to other C-type viral reverse transcriptase by virtue of its p@rence for Mn 2 + activation and certain D NA-RNA hybrid templates, oligo dT12"polyrA (dT12"rA") and oligo da12"polyrC (dG12"rC"), for the stimulation of its activity. The endogenous reaction of the A particle RNA-dependent DNA polymerase produces a DNA transcript of its intrinsic RNA with base com- plementarity as demonstrated by the results of hybridization studies. The control of the expression of this gene entity and its relevance to malignant transformation" constitute a problem worthy o f further investigation. INTRODUCTION NEOPLASTIC transformation has been viewed as a departure from the normal process of differentiation. Frequently the reappearance of fetal characteristics accompanies the onset of the neoplastic state; for example, proteins like serum alpha-fetoprotein and carcino- embryonic antigen can serve as diagnostic markers for hepatocellular carcinoma [1] and carcinoma of the digestive tract [2] respectively. Such phenomena have been attributed to the reactivation of the fetal genes during neoplastic Accepted 19 November 1974. *This work was presented earlier at the Third Con- ference on Embryonic and Fetal Antigens in Cancer, Nov. 4-7, 1973, Oakridge, Tenn., U.S.A. 131 transformation of the cell. Intracisternal A particles (IAP), known primarily for their association with tumors in mice [3-6], gerbils [7], rats [8], and guinea pigs [9], are most probably vertically transmitted from maternal oocyte to fertilized embryo [10, 11]. Their appearance in large numbers during murine preimplantation development has been reported recently [11-13]. In the cell, IAP consist of two concentric shells surrounding a relatively electron lucent core; they measure between 70 and 100 nm in outer diameter when appearing singly (Fig. 1). They are confined exclusively within the cisternae of the endoplasmic reti- culum and are formed by budding at the reticulum membrane [14]. The purposes of this communication are two-fold, 1, to detail the mode of appearance and subsequent fate