CANCER VIROLOGY PROGRAM AREA REPORT
October 1, 1977 to September 30, 1978

Program Coordinators: Dr. Yohei Ito
Dr. Robert McAllister

Administrative Report

MEETINGS, SEMINARS, AND CONFERENCES
The fourth Symposium to convene in this pro-gram area, "The Role of DNA Tumor Viruses in Cancer," was held in Honolulu, Hawaii, May 22 and 23, 1978. The participants were as follows:

For Japan
For the United States
Dr. Y. Ito Dr. R. McAllister
Dr. K. Fujinaga Dr. J. Frankel
Dr. H. Shimojo Dr. J. Stevens
Dr. T. Osato Dr. W. Henle
Dr. Y. Hinuma Dr. W. Eckhart
Dr. S. Kato Dr. M. Botchan
Dr. M. Ishibashi Dr. J. Maizel
G. Kimura Dr. G. Khoury
Dr. M. Martin
Dr. G. Theilan

The participants exchanged information about the mechanisms of oncogenesis by DNA tumor viruses at the molecular and cellular levels in the host. These basic findings were activey discussed in an effort to determine a possible etiologic role of DNA viruses in certain types of cancer in animals and in man.

EXCHANGE OF SCIENTISTS
Drs. John Moloney and Louis Sibal helped arrange a visit to the U.S, by Dr. Akira Seto of the University of Kyoto, September I through December 31, 1977. He visited Dr. R. Herberman (National Cancer Institute), Dr. P. Black (Harvard University), and Dr. G. Pearson (Mayo Clinic).
Dr. Yohei Ito invited Dr. Kenneth Takemoto to visit Japan (University of Tokyo; University of Kyoto; Tohoku University, Sendai; and Kumamoto University) October 3 through October 14, 1977, to give a series of lectures and workshops and to exchange information about human papovaviruses with the Japanese scientists.
Dr. Yoji Ikawa invited Dr. Richard Junghans of the California Institute of Technology to visit several institutions in Japan (Cancer Institute in Tokyo; University of Kyoto, Osaka University) from September 1 through September 23, 1977. Dr. Junghans demonstrated and discussed the heteroduplex mapping technique for nucleic acids.
Following the fourth Symposium in Honolulu in 1978, Dr. J. Frankel of the U.S. gave seminars at four Japanese academic institutes.

EXCHANGE OF MATERIALS
During 1977, plans were made for the Japanese to provide a number of cultured cell lines and for the United States to provide AMV reverse transcriptase and SPF laboratory animals.

Scientific Summary of Program Area
SUMMARY OF YEAR'S ACTIVITIES
Three sessions were held at the East-West Center in Honolulu, May 22 and 23, 1978, where investigators reported work on DNA tumor viruses. The abstracts of the meeting are included in the Five-Year Summary Report which follows this scientific summary.

SPECIFIC OBJECTIVES ACCOMPLISHED
The first four meetings of the two groups have stimulated good collaborative efforts among the Japanese and U.S. scientists. The meetings provided an excellent forum for exchanges of ideas concerning future collaborative cancer research efforts. Also, the personal contacts and mutual respect developed during the four meetings will lead to an enhancement of collaboration between scientists of both countries.
COOPERATIVE AND COLLABORATIVE ACTIVITIES RESULTING FROM PAST MEETINGS AND DISCUSSIONS
The exchange of scientists in both directions and the relaxed interactions at the four joint meetings are tangible evidence of the remarkable good will developed between our two countries.

Five-Year Summary Report, 1974 to 1978
ADMINISTRATIVE REPORT
Meetings, Seminars, and Conferences
The first Symposium on DNA and RNA tumor viruses, "Recent Advances in Tumor Virology," took place in Hilo, Hawaii, March 22 and 23, 1975. The participants were as follows:

For Japan
For the United States
Dr. Y. Ito Dr. R. McAllister
Dr. H. Shimojo Dr. J. Bishop
Dr. K. Fujinaga Dr. M. Gardner
Dr. I. Osato Dr. T. August
Dr. Y. Ikawa Dr. F. Rapp
Dr. H. Yoshikura Dr. W. Eckhart

Scientific sessions were devoted to papers and lively discussions of five classes of tumor viruses.
Presentations concerning DNA tumor viruses described the transforming activities and other gene functions of polyoma and SV-40 viruses. Studies of human adenovirus genomes in transformed hamster cells were reported. Cellular transformation by Epstein-Barr virus and by herpes simplex viruses were described as was the use of the Shope papilloma-carcinoma complex as a model for human cancer research.
Presentations concerning RNA tumor viruses included descriptions of the avian virus-host cell interactions. The natural history of the wild mouse type-C viruses and the host range and effects upon cellular differentiation by laboratory strains of mouse virus were reported. The characteristics of RD-114 virus in its extracellular type-C virus and intracellular DNA proviral forms were presented. The genetic expressions in mouse and human cells of type-C viral proteins and of infective viruses were also described.
Planning sessions were devoted to lengthy discussions addressing the general topic of how to effectively advance our knowledge of viruses in human carcinogenesis. Exchange of scientists, preprints, and materials were discussed, as were the topics and site for the next meeting of the Cancer Virus Groups. It was proposed that ex-changes of preprints and reprints be on an individual scientist-to-scientist basis. Requests for materials should funnel through the Program Coordinators to their sources in each country. The second Symposium, "Viral Oncogenesis Transmission, Persistence, and Expression of Viral Genome," was held in Kyoto, Japan, March 26 and 27, 1976. The participants were as follows:

For Japan
For the United States
Dr. M. Ishibashi Dr. W. Eckhart
Dr. T. Miyamoto Dr. J. Maizel
Dr. S. Kawai Dr. J. Bishop
Dr. K. Toyoshima Dr. P. Vogt
Dr. H. Yoshikura Dr. M. Gardner
Dr. S. Kato Dr. R. Gallo
Dr. T. Osato Dr. R. McAllister
Dr. Y. Ito

Three sessions were held at the Miyako Hotel on March 26 and 27, 1976. The investigators reported work on the entire spectrum of cancer viroiogy, on culture of human cancer cells, and on possible interrelationships of chemical and viral carcinogenesis. The newest data were presented on the major groups of cancer viruses, namely, papovaviruses, adenoviruses, herpes viruses, and type-C RNA tumor viruses. These presentations ranged from basic molecular virology to implications of cancer in wild mice and humans, and the description of type-C viruses recovered from human acute myelocytic leukemia cells.
Drs. Hakura, Eckhari, and Kimura described the transforming and other gene functions of polyoma and SV-40 viruses as well as the relation between viral genes and host cells. Drs. Fujinaga, Shimojo, Ishibashi, and Maizel discussed the adenovirus proteins and viral genes in adenovirus-transformed cells. Drs. Miyamoto, Kawai, Bishop, Toyoshima, and Vogt discussed the genetics and physiology of avian type-C virus-cell interactions. Dr. Yoshikura discussed the role of chemical car-cinogenesis in the induction of endogenous murine type-C virus. Dr. Gardner discussed the role of ecotropic and amphotropic type-C viruses in the pathogenesis of lymphoma and paralysis of wild mice in Los Angeles. Dr. Kato reported the establishment of Mareks lymphoma cell lines and the expression of herpes and type-C viruses in these lines. Dr. Osato discussed the possible influence of murine type-C virus upon the expression of Epstein-Barr virus in human cells. Dr. Gallo defined the relation between the woolly monkey and baboon type-C viruses and viruses from a patient with acute myelocytic leukemia. Dr. McAllister described the structure of RD-114 viral RNA and infectivity of viral DNAs from human and cat cells. And, Dr. Ito reported the properties of two lines of cells he established from human nasopharyngeal carcinomas.
The third Symposium, "Origin and Function of Oncogenic Sequences in RNA Tumor Viruses," was conducted in Pasadena, California, May 31 and June 1, 1977. The participants were as follows:

For Japan
For the United States
Dr. Y. Ito Dr. R. McAllister
Dr. Y. Ikawa Dr. N. Davidson
Dr. T. Yamamoto Dr. M. Gardner
Dr. K. Toyoshima Dr. D. Spector
Dr. T. Miyamoto Dr. P. Besmer
Dr. M. Yoshida Dr. P. Duesberg
Dr. T. Odaka Dr. T. Shih
Dr. N. Tsuchida (observer) Dr. J. Frankel

During these sessions, the participants reported on current and often unpublished studies about the origin, structure, and function of avian and mam-malian RNA tumor viral genes.
The fourth Symposium, "Role of DNA Tumor Viruses in Cancer," was held May 22 and 23, 1978, in Honolulu, Hawaii. The participants were as follows:

For Japan
For the United States
Dr. Y. Ito Dr. R. McAllister
Dr. K. Fujinaga Dr. J. Frankel
Dr. H. Shimojo Dr. J. Stevens
Dr. T. Osato Dr. W. Henle
Dr. Y. Hinuma Dr. W. Eckhart
Dr. S. Kato Dr. M. Botchan
Dr. M. Ishibashi Dr. J. Maizel
Dr. G. Kimura Dr. G. Khoury
Dr. M. Martin
Dr. G. Theilan

The participants exchanged information about the mechanisms of oncogenesis by DNA tumor viruses at the molecular and cellular levels in the host. These basic findings were actively discussed in an effort to determine a possible etiologic role of DNA viruses in certain types of cancer in animals and in man.

Exchange of Scientists
During the Spring and Summer of 1975, Dr. Fumio Mizuno worked at the National Cancer Institute, Bethesda, Maryland, and the Presbyterian-Rush Medical School, Chicago, Illinois.
Before and after the second Symposium in Kyoto in 1976, seven American scientists visited nine institutions in Japan to exchange information, to give thirteen seminars, and to make plans for collaborative projects and for possible exchange visits. These visits are outlined below:
Dr. Walter Eckhart. Department of Tumor Virus Research, Institute of Medical Sciences, University of Tokyo; Department of Microbiology, University of Kyoto; Department of Virology and Bacteriology, Tottori University School of Medicine; and Department of Tumor Viruses, Research Institute for Microbial Diseases, Osaka University.
Dr. Peter Vogt. Department of Tumor Viruses, Research Institute for Microbial Diseases, Osaka University; Department of Biochemistry, Cancer Institute, Okayama University School of Medicine; Department of Microbiology, Kumamoto University School of Medicine; and Department of Tumor Virus Research, Institute of Medical Sciences, University of Tokyo.
Dr. Robert Gallo. Department of Microbiology, Kyoto University.
Dr. J. Michael Bishop. Department of Micro-biology, Kyoto University; Department of Tumor Viruses, Institute for Microbial Diseases, Osaka University; and Institute for Cancer Research, University of Tokyo.
Drs. Murray Gardner and Robert McAllister. Radiation Effects Research Foundation, Hiroshima.
Dr. Jacob Maizel. Department of Microbiology, Osaka University.
A number of collaborative endeavors are underway. Dr. Hakura (from Dr. Toyoshima's laboratory) and Dr. Kimura (of Tottori University) will conduct experiments with Dr. Eckhart. Drs. Fumio Mizuno and Masahide Ishibashi conducted experiments in the United States. Dr. Oda's group discussed their plans for avian tumor virus research with Dr. Vogt. Other scientists from both sides are considering collaborative ventures and possible ex-change visits.
Before the third Symposium in Pasadena in 1977, Drs. Y. Ikawa, M. Yoshida, and K. Toyoshima attended and presented papers at the Cold Spring Harbor meeting "RNA Tumor Viruses." After the Pasadena meeting, some Japanese scientists visited the University of Southern California, the California Institute of Technology, and the National Cancer Institute to exchange information, to give seminars, and to make plans for collaborative projects and possible exchange visits.
Drs. John Moloney and Louis Sibal helped arrange a visit to the U.S. by Dr. Akira Seto of the University of Kyoto, September 1 through December 31, 1977. He visited Dr. R. Herberman (National Cancer Institute), Dr. P. Black (Harvard University), and Dr. G. Pearson (Mayo Clinic).
Dr. Yohei Ito invited Dr. Kenneth Takemoto to visit Japan (University of Tokyo; University of Kyoto; Tohoku University, Sendai; and Kumamoto University) October 3 through October 14, 1977, to give a series of lectures and workshops and to exchange information about human papovaviruses with the Japanese scientists.
Dr. Yoji Ikawa invited Dr. Richard Junghans of the California Institute of Technology to visit several institutions in Japan (Cancer Institute, Tokyo; University of Kyoto; Osaka University) from September 1 through September 23, 1977.
Dr. Junghans demonstrated and discussed the heteroduplex mapping technique for nucleic acid.
Following the fourth Symposium in Honolulu in 1978, Dr. J. Frankel, of the United States, gave seminars at four Japanese academic institutes.

Exchange of Resources and Materials
Over the past five years, the following materials were exchanged between scientists from Japan and the U.S.:
In 1975, a set of materials requested by Dr. Yoji Ikawa was sent to him by the office of Pro-gram Resources and Logistics, National Cancer Institute. During 1976, 500 ml of erythro-poietin from a pool which is ARG-567-Ta LSL (this pool had a specific activity of 52.7 units per mg.) was sent by Dr. Peter Dukes to Dr. Ikawa for his research work on induction of differentiation of Friend virus-induced leukemia cells.
Dr. Ikawa also received from Dr. Jack Gruber avian myeloblastosis virions and antisera to type-C viruses. These were used by him and by Drs. T. Osato, K. Fujinaga, and others for studies of viral etiology of human cancer.
Dr. G. Kimura gave his 3Y-1 rat cell line to Dr. W. Eckhart for studies of virus-induced trans-formation.
During 1977, plans were made for the Japanese to provide a number of cultured cell lines and the U.S. to provide AMV reverse transcriptase and SPF laboratory animals.

SCIENTIFIC SUMMARY OF PROGRAM AREA
Extent and Manner in Which Cooperative Activities Have Provided Impact or Influence on the Two Countries
During our mutual interaction over the past five years, scientists from Japan and the U.S. have developed a mutual respect and quiet confidence in each other that will lead to ever-widening areas of scientific cooperation, in the mutual exchange of scientists (both senior and junior), preprints, and materials.
Subsequent developments depend upon maintaining and widening the respect and cooperation that have been established during our five year collaboration. In the future, we must continue our pre-sent annual interaction and, specifically, include young scientists from both countries who will carry these achievements of mutual respect into the future.