ADVANCESINCANCERRESEARCH VOLUME 40 Contributors to This Volume Vladimir N. Anisimov Daniel Meruelo Richard Bach Cathleen T. Moore Gosta Gahrton Dan H. Moore Peter A. Jones Dan H. Moore II H. Kirchner Arthur D. Riggs Howard E. Skipper ADVANCES IN CANCERRESEARCH Edited by GEORGE KLEIN Department of Tumor Biology Karolinska lnstitutet Stockholm, Sweden SIDNEY WEINHOUSE Fels Research Institute Temple University Medical School Philadelphia, Pennsylvania Volume 40- 1983 ACADEMIC PRESS A Subsidiary of Harcourt Brace Jovanovich, Publishers New York London Paris San Diego San Francisco Slo Paulo Sydney Tokyo Toronto COPYRIGHT @ 1983, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECtlANICAL, INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATlON STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. 111 Fifth Avenue, New Yark, New York 10003 United Kingdoit2 Edition published by ACADEMIC PRESS, I N C . (LONDON) LTD. 24/28 Oval Road, London N W l 7DX LIBRARY OF CONGRESS CATALOG CARDNUMBER: 52 ISBN 0 - 1 2 - 0 0 6 6 4 0 - 8 PRlNTED IN THE UNITED STATES OF AMERICA 83 84 85 86 9 X 7 6 5 4 3 2 1 - 1 3360 CONTENTS CONTRIBUTORS TO VOLUME 40 ........................ iX 5.Methylcytosine. Gene Regulation. and Cancer . ARTHURD RIGGSAND PETERA . JONES I. I1. 111. IV. V. VI . VII . VIII. IX . X. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . Basic Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . Evidence for Gene Regulation by DNA Modification . . . . . . . . . Cause or Effect: Necessary but Not Sufficient . . . . . . . . . . . . Induction of Gene Expression by 5-Azacytidine . . . . . . . . . . . Cancer-A Disease Resulting from Abnormal Differentiation . . . . . 5-Methylcytosine Levels in Tumorigenic Cells . . . . . . . . . . . . Carcinogens and Enzymatic DNA Methylation . . . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 3 6 10 11 14 15 18 22 23 25 lmmunobiology of Infection with Human Cytomegalovirus H . KIRCHNER I. I1. I11. IV. V. VI VII . VIII . IX. X. XI * XI1 XI11. XIV . . . xv. XVI. XVII . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . Herpesviruses . . . . . . . . . . . . . . . . . . . . . . . . . . . Cytomegaloviruses. HCMV . . . . . . . . . . . . . . . . . . . . . HCMV-Host Cell Interactions . . . . . . . . . . . . . . . . . . . . Epidemiology of the Infection with HCMV . . . . . . . . . . . . . . Diagnosis of HCMV Infection . . . . . . . . . . . . . . . . . . . . Clinical Significance of HCMV Infections . . . . . . . . . . . . . . Oncogenic Potential of HCMV. . . . . . . . . . . . . . . . . . . . Immunopathology . . . . . . . . . . . . . . . . . . . . . . . . . LatencyIReactivation . . . . . . . . . . . . . . . . . . . . . . . . Replication of HCMV in Leukocytes . . . . . . . . . . . . . . . . . Effects of HCMV on Leukocytes . . . . . . . . . . . . . . . . . . . Immunity against Infections with HCMV. General Aspects . . . . . . Humoral Immune Responses . . . . . . . . . . . . . . . . . . . . Cell-Mediated Immunity . . . . . . . . . . . . . . . . . . . . . . Nonspecific Defense Mechanisms against HCMV Infection . . . . . . Vaccine and Therapy Problems . . . . . . . . . . . . . . . . . . . V 32 35 37 39 41 45 47 55 61 63 64 67 69 72 76 83