Abstract
Data from a previous study of the cytogenetic effects, in cultured lymphocytes, of exposure to the atomic bomb in Hiroshima have been reanalyzed to determine the relationship between the occurrence of "rogue" cells in an individual and the frequency of "simple" chromosomal damage in the nonrogue cells of the same individual. Rogue cells are cells with complex chromosomal damage, currently believed to be a manifestation of the activity of a human polyoma virus termed "JC." Among a total of 1,835 persons examined, there were 45 exhibiting rogue cells. A total of 179,599 cells were scored for simple chromosomal damage. In both the exposed and the control populations, there was an absolute increase of approximately 1.5% in the frequency of simple chromosomal damage in the nonrogue cells of those exhibiting rogue cells, when compared with the frequencies observed in those not exhibiting rogue cells, which is a statistically significant difference. It is argued that this phenomenon, occurring not only in lymphocytes but possibly also in other cells/tissues, may play a contributory role in the origin of malignancies characterized by clonal chromosome abnormalities. Unexpectedly, among those exhibiting rogue cells, there was a disproportionately greater representation of persons who had received relatively high radiation exposures from the bomb. The reason for this is unclear, but it is tempting to relate the finding to some lingering effect of the exposure (or the circumstances surrounding the exposure) on immunocompetence.
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- Akiyama M. Late effects of radiation on the human immune system: an overview of immune response among the atomic-bomb survivors. Int J Radiat Biol. 1995 Nov;68(5):497–508. doi: 10.1080/09553009514551491. [DOI] [PubMed] [Google Scholar]
- Awa A. A., Honda T., Sofuni T., Neriishi S., Yoshida M. C., Matsui T. Chromosome-aberration frequency in cultured blood-cells in relation to radiation dose of A-bomb survivors. Lancet. 1971 Oct 23;2(7730):903–905. doi: 10.1016/s0140-6736(71)92505-0. [DOI] [PubMed] [Google Scholar]
- Awa A. A., Neel J. V. Cytogenetic "rogue" cells: what is their frequency, origin, and evolutionary significance? Proc Natl Acad Sci U S A. 1986 Feb;83(4):1021–1025. doi: 10.1073/pnas.83.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Awa A. A. Persistent chromosome aberrations in the somatic cells of A-bomb survivors, Hiroshima and Nagasaki. J Radiat Res. 1991 Mar;32 (Suppl):265–274. doi: 10.1269/jrr.32.supplement_265. [DOI] [PubMed] [Google Scholar]
- Awa A. A., Sofuni T., Honda T., Itoh M., Neriishi S., Otake M. Relationship between the radiation dose and chromosome aberrations in atomic bomb survivors of Hiroshima and Nagasaki. J Radiat Res. 1978 Jun;19(2):126–140. doi: 10.1269/jrr.19.126. [DOI] [PubMed] [Google Scholar]
- Bloom A. D., Neel J. V., Choi K. W., Iida S., Chagnon N. Chromosome aberrations among the Yanomamma Indians. Proc Natl Acad Sci U S A. 1970 Jul;66(3):920–927. doi: 10.1073/pnas.66.3.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bloom A. D., Neel J. V., Tsuchimoto T., Meilinger K. Chromosomal breakage in leukocytes of South American Indians. Cytogenet Cell Genet. 1973;12(3):175–186. doi: 10.1159/000130453. [DOI] [PubMed] [Google Scholar]
- Bochkov N. P., Katosova L. D. Analysis of multiaberrant cells in lymphocytes of persons living in different ecological regions. Mutat Res. 1994 Jan-Feb;323(1-2):7–10. doi: 10.1016/0165-7992(94)90038-8. [DOI] [PubMed] [Google Scholar]
- Coleman D. V., Wolfendale M. R., Daniel R. A., Dhanjal N. K., Gardner S. D., Gibson P. E., Field A. M. A prospective study of human polyomavirus infection in pregnancy. J Infect Dis. 1980 Jul;142(1):1–8. doi: 10.1093/infdis/142.1.1. [DOI] [PubMed] [Google Scholar]
- Dyson N., Bernards R., Friend S. H., Gooding L. R., Hassell J. A., Major E. O., Pipas J. M., Vandyke T., Harlow E. Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol. 1990 Mar;64(3):1353–1356. doi: 10.1128/jvi.64.3.1353-1356.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fanning E., Knippers R. Structure and function of simian virus 40 large tumor antigen. Annu Rev Biochem. 1992;61:55–85. doi: 10.1146/annurev.bi.61.070192.000415. [DOI] [PubMed] [Google Scholar]
- Fox D. P., Robertson F. W., Brown T., Whitehead A. R., Douglas J. D. Chromosome aberrations in divers. Undersea Biomed Res. 1984 Jun;11(2):193–204. [PubMed] [Google Scholar]
- Grinnell B. W., Padgett B. L., Walker D. L. Distribution of nonintegrated DNA from JC papovavirus in organs of patients with progressive multifocal leukoencephalopathy. J Infect Dis. 1983 Apr;147(4):669–675. doi: 10.1093/infdis/147.4.669. [DOI] [PubMed] [Google Scholar]
- Harris K. F., Christensen J. B., Imperiale M. J. BK virus large T antigen: interactions with the retinoblastoma family of tumor suppressor proteins and effects on cellular growth control. J Virol. 1996 Apr;70(4):2378–2386. doi: 10.1128/jvi.70.4.2378-2386.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson A. L., Loeb L. A. The mutation rate and cancer. Genetics. 1998 Apr;148(4):1483–1490. doi: 10.1093/genetics/148.4.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lazutka J. R. Chromosome aberrations and rogue cells in lymphocytes of Chernobyl clean-up workers. Mutat Res. 1996 Mar 9;350(2):315–329. doi: 10.1016/0027-5107(95)00170-0. [DOI] [PubMed] [Google Scholar]
- Lazutka J. R., Neel J. V., Major E. O., Dedonyte V., Mierauskine J., Slapsyte G., Kesminiene A. High titers of antibodies to two human polyomaviruses, JCV and BKV, correlate with increased frequency of chromosomal damage in human lymphocytes. Cancer Lett. 1996 Dec 3;109(1-2):177–183. doi: 10.1016/s0304-3835(96)04448-5. [DOI] [PubMed] [Google Scholar]
- Lehman J. M. Early chromosome changes in diploid Chinese hamster cells after infection with Simian virus 40. Int J Cancer. 1974 Feb 15;13(2):164–172. doi: 10.1002/ijc.2910130203. [DOI] [PubMed] [Google Scholar]
- Loeb L. A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991 Jun 15;51(12):3075–3079. [PubMed] [Google Scholar]
- MOORHEAD P. S., NOWELL P. C., MELLMAN W. J., BATTIPS D. M., HUNGERFORD D. A. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 1960 Sep;20:613–616. doi: 10.1016/0014-4827(60)90138-5. [DOI] [PubMed] [Google Scholar]
- Major E. O., Amemiya K., Tornatore C. S., Houff S. A., Berger J. R. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 1992 Jan;5(1):49–73. doi: 10.1128/cmr.5.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neel J. V., Awa A. A., Kodama Y., Nakano M., Mabuchi K. "Rogue" lymphocytes among Ukrainians not exposed to radioactive fall-out from the Chernobyl accident: the possible role of this phenomenon in oncogenesis, teratogenesis, and mutagenesis. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6973–6977. doi: 10.1073/pnas.89.15.6973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neel J. V., Major E. O., Awa A. A., Glover T., Burgess A., Traub R., Curfman B., Satoh C. Hypothesis: "Rogue cell"-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2690–2695. doi: 10.1073/pnas.93.7.2690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierce D. A., Shimizu Y., Preston D. L., Vaeth M., Mabuchi K. Studies of the mortality of atomic bomb survivors. Report 12, Part I. Cancer: 1950-1990. Radiat Res. 1996 Jul;146(1):1–27. [PubMed] [Google Scholar]
- Ray F. A., Kraemer P. M. Iterative chromosome mutation and selection as a mechanism of complete transformation of human diploid fibroblasts by SV40 T antigen. Carcinogenesis. 1993 Aug;14(8):1511–1516. doi: 10.1093/carcin/14.8.1511. [DOI] [PubMed] [Google Scholar]
- Ray F. A., Meyne J., Kraemer P. M. SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts. Mutat Res. 1992 Dec 16;284(2):265–273. doi: 10.1016/0027-5107(92)90011-p. [DOI] [PubMed] [Google Scholar]
- Ray F. A., Peabody D. S., Cooper J. L., Cram L. S., Kraemer P. M. SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts. J Cell Biochem. 1990 Jan;42(1):13–31. doi: 10.1002/jcb.240420103. [DOI] [PubMed] [Google Scholar]
- Rencic A., Gordon J., Otte J., Curtis M., Kovatich A., Zoltick P., Khalili K., Andrews D. Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7352–7357. doi: 10.1073/pnas.93.14.7352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salomaa S., Sevan'kaev A. V., Zhloba A. A., Kumpusalo E., Mäkinen S., Lindholm C., Kumpusalo L., Kolmakow S., Nissinen A. Unstable and stable chromosomal aberrations in lymphocytes of people exposed to Chernobyl fallout in Bryansk, Russia. Int J Radiat Biol. 1997 Jan;71(1):51–59. doi: 10.1080/095530097144418. [DOI] [PubMed] [Google Scholar]
- Stewart N., Bacchetti S. Expression of SV40 large T antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells. Virology. 1991 Jan;180(1):49–57. doi: 10.1016/0042-6822(91)90008-y. [DOI] [PubMed] [Google Scholar]
- Stram D. O., Sposto R., Preston D., Abrahamson S., Honda T., Awa A. A. Stable chromosome aberrations among A-bomb survivors: an update. Radiat Res. 1993 Oct;136(1):29–36. [PubMed] [Google Scholar]
- Swenson J. J., Trowbridge P. W., Frisque R. J. Replication activity of JC virus large T antigen phosphorylation and zinc finger domain mutants. J Neurovirol. 1996 Apr;2(2):78–86. doi: 10.3109/13550289609146541. [DOI] [PubMed] [Google Scholar]
- Tawn E. J., Cartmel C. L., Pyta E. M. Cells with multiple chromosome aberrations in control individuals. Mutat Res. 1985 Dec;144(4):247–250. doi: 10.1016/0165-7992(85)90059-4. [DOI] [PubMed] [Google Scholar]
- Tawn E. J. The frequency of chromosome aberrations in a control population. Mutat Res. 1987 Dec;182(6):303–308. doi: 10.1016/0165-1161(87)90072-0. [DOI] [PubMed] [Google Scholar]
- Tominaga T., Yogo Y., Kitamura T., Aso Y. Persistence of archetypal JC virus DNA in normal renal tissue derived from tumor-bearing patients. Virology. 1992 Feb;186(2):736–741. doi: 10.1016/0042-6822(92)90040-v. [DOI] [PubMed] [Google Scholar]
- Tornatore C., Berger J. R., Houff S. A., Curfman B., Meyers K., Winfield D., Major E. O. Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy. Ann Neurol. 1992 Apr;31(4):454–462. doi: 10.1002/ana.410310426. [DOI] [PubMed] [Google Scholar]
- Verschaeve L., Domracheva E. V., Kuznetsov S. A., Nechai V. V. Chromosome aberrations in inhabitants of Byelorussia: consequence of the Chernobyl accident. Mutat Res. 1993 Jun;287(2):253–259. doi: 10.1016/0027-5107(93)90018-b. [DOI] [PubMed] [Google Scholar]
- WOLMAN S. R., HIRSCHHORN K., TODARO G. J. EARLY CHROMOSOMAL CHANGES IN SV40-INFECTED HUMAN FIBROBLAST CULTURES. Cytogenetics. 1964;3:45–61. doi: 10.1159/000129797. [DOI] [PubMed] [Google Scholar]