76 



ARTHUR C. UPTON 



"control" genes (or their genetic equivalents) one of which is generally 

 inherited. The Ph^ chromosome is regarded as a deletion or translocation and 

 equivalent to one mutation. He claims that the age-dependence and the dose- 

 response relation for non-leukaemic malignancies induced at Hiroshima can 



Table V. Incidence of chronic myeloid leukaemia and frequency of spontaneous 

 and radiogenic human chrotnosome aberrations f 



Parameter 



Rate 



Chromosome deletions 

 Spontaneous 

 Radiogenic 



Chromatid and isochromatid deletions 

 Spontaneous 

 Radiogenic 



Deletions of chromosome-21 per cell at risk 

 Spontaneous 

 Radiogenic 



Number of myeloblasts at risk per person 



Deletions of chromosome-21 per marrow 

 Spontaneous 

 Radiogenic 



Incidence of chronic myeloid leukaemia 

 Spontaneous 



Radiogenic 



<^ 2-4 X 10"' per cell (in one cell generation) 

 /^ 1-1 X 10~' per cell (in one cell generation/r) 



< 2-4 X 10"^ per cell (in one cell generation) 

 '■»-' 2-2 X 10"' per cell (in one cell generation/r) 



<^ 3-1 X 10"^ per cell (in one cell generation) 

 /"^ 1-9 X 10"' per cell (in one cell generation/r) 



1-0 X 10" (Brues, 1959) 



'^-' 1-1 X 10* per person (per year) 

 ' — ' 1-9 X 10* per person (per r) 



'-^ 0-3-8 X 10"^ per person (per year) 



(Court Brown and Doll, 1959, 1960) 

 > 0-3-8 X 10"^ per person (per r) 



t The rates of spontaneous and radiogenic chromosome and chromatid deletions were 

 derived with the help of M. A. Bender from data on human nucleated blood cells irradiated 

 in vitro (Bender and Gooch, 1962 and unpublished). The frequency per cell of deletions that 

 could yield a Ph^ chromosome was estimated by correcting the combined chromosomal 

 detection frequencies to adjust for that fraction of the total length of chromosomal material at 

 risk; i.e. for the average length of the 21st and 22nd pair, of 1-4% of the total. It is recognized, 

 however, that this correction fails to allow for the specificity and viability of the deletion 

 within the 21st or 22nd chromosome yielding the Ph^ chromosome; hence, the frequencies 

 predicted are undoubtedly too high by an unknown, but probably large, margin. In estimating 

 the radiogenic chromosomal deletion frequencies, the rates of chromosome and chromatid 

 types were weighted to allow for the portions of the cell cycle occupied by the single- and 

 double-stranded stages; i.e. estimated to be 75% and 25%, respectively. The frequency of 

 such delections per person in one year was estimated by multiplying the deletion frequency per 

 cell times the number of cells (presumably myeloblasts) at risk (1 X lO^^) times the number of 

 cell generations per year (arbitrarily assumed to be 365). 



be interpreted in detail by assuming that radiation simulates the spon- 

 taneous mutation process. However, at high dose and dose-rate, he suggests 

 a more efficient mechanism may be responsible for the high radiogenic 



