PEELIMINAKY STUDIES ON LATE SOMATIC EFFECTS OF 

 EADIOMIMETIC CHEMICALS 



A. C. UPTON, J. W. CONKLIN, T. P. McDONALD, and 

 K. W. CHRISTENBERRY 



Biology Division, Oak Ridge National Laboratory ,'\ Oak Ridge, Tennessee, U.S.A. 



SUMMARY 



The life-span of mice surviving mid-lethal doses of nitrogen mustard (HN2), 

 triethylene melamine (TEM), and X-rays was reduced. The extent of life shortening was 

 greatest in the irradiated mice, intermediate in the TEM-treated animals, and smallest 

 in those given HN2. 



The decrease in longevity was not ascribable to any single lesion or group of lesions 

 but was associated with premature onset of diseases of senescence. Moreover, mice 

 without neoplasms died as early as those with neoplasms. 



AU tliree agents increased the mcidence of certain neoplastic growths, but the onco- 

 genic effects varied from one organ to another, no two agents affecting all organs similarh^ 



Lens opacities were induced by each agent. However, those in the HN2-injected 

 mice were barely distinguishable from spontaneously occurring senUe cataracts. 



Although, late effects of ionizing radiation on the life-span and on the 

 incidence of neoplastic and other diseases have been recognized for years, there 

 is little information concerning the physico-chemical and biochemical changes 

 responsible for initiating such effects. Attempts to reproduce them with radio- 

 mimetic chemicals have led to conflicting conclusions (see Curtis and Gebhard, 

 1959; Alexander and Connell, 1960; Stevenson and Curtis, 1961). The present 

 study was undertaken, therefore to exj)lore systematically the somatic effects 

 of several radiomimetic chemicals compared to X-rays. 



Preliminary results from one phase of this investigation are presented 

 here. 



METHODS 



Female RF/Up mice were subjected to 500-600 r of whole-body X- 

 radiation, triethylene melamine (TEM), or nitrogen mustard (HN2) at 10 

 weeks of age (Table I). The factors of irradiation were as follows: 250 kVp; 

 30 mA; TSD, 93-7 cm; hvl, O-U mm Cu; dose-rate, 80-90 r/min with 

 maximum scatter. TEM was administered intraperitoneally, 3-0 to 4-0 

 mg/kg, as an 0-03 to 0-04% solution in physiological saline. HN2 was 

 administered intravenously in the form of methyl bis-(jS-chloroethyl)amine, 



t Operated by Union Carbide Corporation for the United States Atomic Energy Commission. 



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