Overture
Cytogenetics: Chromosomes are basic building blocks of DNA and present linkage groups of genes.
Cytogenetics was first coined by merging cytology and genetics from studies of W. S. Sutton in 1903 on the mitoticand meiotic behavior of chromosomes in grasshopper as the science of chromosomes. Combined with theobservations of Th. Boveri (1902) in fertilization in sea urchin eggs, the principle of chromosome behavior is now
often called Sutton-Boveri Chromosomal Theory of Inheritance.
Radiation cytogenetics: What is mutation? The central problem of mutation was opened up by the epochal
discovery of H. J. Muller (1927) that X-rays dramatically increased mutations in Drosophila, in which dominantlethal mutations, incomplete recessive mutations and gross chromosomal rearrangements were suggested. Similarly,B. McCrintock (1931) studied X-ray-induced mutation in plants, maize and Nicotiana and concluded that “None of
the recessive phenotypes in the examined plants arose from gene mutation. Each reflected loss of a segment ofchromosome that carried the wild-type allele, and x-rays were responsible for inducing these deficiencies”(McClintock 1984). It is currently accepted that the expression of recessive mutation by radiation is mostly aconsequence of a loss of allele by chromosomal mechanisms, deletion or mitotic recombination (Sankaranarayanan
1991a, 1991b). The direct cytological evaluation of radiation-induced chromosome aberrations was first made by K.
Sax and his colleagues (Sax 1938, 1939, 1940, 1941) in the mitotic and meiotic chromosomes of Tradescantia
microspores. The action of X-rays on chromosomes revealed in these early days has continued to provide afundamental concept of modern radiation cytogenetics.
Human radiation cytogenetics:

Advances in the methods of tissue culture (Hsu and Pomerat 1953) andchromosome preparation (Makino and Nishimura 1952), opened the daybreak of modern human cytogenetics. The
normal set of chromosomes of man was determined by Tjio and Levan (1956). Aided by the development of culture
method of peripheral blood lymphocyte by Moorhead et al. (1969), there became burst of “clinical cytogenetics”,
dealing with inborn errors of chromosome, such as Down syndrome (Lejeune et al. 1959), Turner syndrome (Ford etal. 1959) and Klinefelter syndrome (Jacobs and Strong 1959). When the chromosome methods became available forhuman material, it soon became clear that chromosome aberrations were produced in the cells of radiation treatedhumans (Tough et al. 1960, Sasaki 1961, Buckton et al. 1962). The “human radiation cytogenetics” evolved as a partof human cytogenetics that concerns the effects of radiation in humans (e.g., Bender 1969).
Radiation dose assessment by chromosome aberration analysis: As to the radiation-induced chromosomeaberrations, we have large amount of legacies from over 30 years’ studies in plant materials, including the effects ofdose and dose-rate, quality of radiation, and cell-cycle position at irradiation. Evidence has been accumulated to showthat human chromosomes respond similarly to that of plants. The extensive review was first made on this issue by theUnited Nations Scientific Committee of the Effects of Atomic Radiation (UNSCEAR) in 1969, in which the use ofchromosome aberration analysis was suggested to be a practical application in the biological dose assessment in thehuman radiation exposure. Currently, chromosome aberration analysis is considered to provide most reliable meansfor dose assessment in the radiation exposed persons. The standardization of the method may be seen in the reports ofthe International Atomic Energy Agency (IAEA).

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Muller, H. J. Artificial transmutation of the gene. Science, 66, 84-87, 1927.
McClintock, B., The origin and behavior of mutable loci in maize. Proc. Natl. Acad. Sci. USA, 36:344-355, 1950.
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mammalian in vivo systems. Mut. Res., 258: 51-73, 1991a.
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mutations in mammalian in vitro systems and mechanisms of mutations by radiation. Mut. Res., 258: 75-97,
1991b.
Sax, K. Chromosome aberrations induced by X-rays. Genetics, 23, 494-516, 1938.
Sax, K. The time factor in x-ray production of chromosomal aberrations. Proc. Natl. Acad. Sci., USA., 25, 225-233,1939.
Sax, K. An analysis of x-ray induced chromosomal aberrations in Tradescantia. Genetics, 25, 41-68, 1940.
Sax, K. Types and frequencies of chromosome aberrations induced by X-rays. Cold Spring Harbor Symposium on
Quantitative Biology, 9, 93-101, 1941.
Hsu, T. C. and C. M. Pomerat, Mammalian chromosomes in vitro. II. A method for spreading the chromosomes ofcells in tissue culture. J. Hered., 44: 23-29, 1953.
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study of animals. Stain Tech., 27: 1-7, 1952.
Tjio, J. H. and A. Levan, The chromosome number of man. Hereditus, 42: 1-6, 1956.
Moorhead, P. S. et al. Chromosome preparations of leukocytes cullcuted from human peripheral blood. Exp. Cell Res.,
20: 613-616, 1960.
Lejeune, J., M. Gautier, and R. Turpin, Etude fes chromosomes somatiques de neuf enfant mongoliens. Compt. Rend.,
248: 1721-1722, 1959.
Ford, C. E. et al. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner’s syndrome). Lancet, i:711-713, 1959.
Jacobs, P. A. and J. A. Strong, A case of human intersexuality having a possible XXY sex-determining mechanism.
Nature, 210: 352-354, 1959.
Tough, I. M. et al. X-ray-induced chromosome damage in man. Lancet, ii: 849-851, 1960.
Sasaki, M. S., Cytological effect of chemicals on tumors. XII. A chromosome study in human gastric tumor following
radioactive colloid gold (Au198) treatment. J. Fac. Sci. Hokkaido Univ., Ser. VI, Zool., 14: 566-75, 1961.
Buckton, K. E. et al. A study of the chromosome damage persisting after X-ray therapy for ankylosing spondylitis.
Lancet, ii: 676-682, 1962.
Bender, M. A, Human Radiation Cytogenetics. Advances in Radiation Biology. Vol 3, Academic Press, New York,
pp.215-275, 1969.

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UNSCEAR. Radiation-induced chromosome aberrations in human cells. In: Report of the United Nations ScientificCommittee on the Effects of Atomic Radiation. Annex C. United Nations. 1969.
IAEA. Biological dosimetry: Chromosomal aberration analysis for dose assessment. International Atomic Energy
Agency. Technical Reports Series 260, 1986.
IAEA. Cytogenetic analysis for radiation dose assessment. A manual. International Atomic Energy Agency. TechnicalReports Series 405. 2001.
IAEA. Cytogenetic dosimetry: Applications in preparedness for and response to radiation emergencies. International
Atomic Energy Agency. 2011.
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Compiled by Masao S. Sasaki, D.Sc.

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