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Disposition and metabolic fate of carbon 14 ethylnitrosourea in rat


Medical Journal of Kobe University 45(4): 25-38
Disposition and metabolic fate of carbon 14 ethylnitrosourea in rat
The distribution of (14C-ethyl) and (14C-urea) ethylnitrosourea [ENU] in organs of young female and fetal SD-JCL rats of late gestational age was studied after i.v. and transplacental applications, respectively. Subcellular distribution in the liver, kidney and brain was also investigated. In young female rats, the activity of ethyl-14C was most prominent in the liver, kidney and lung shortly after administration, and decreased uniformly, but slowly in all organs after 12 h. Urea-14C activity, in contrast, was especially high in the kidney in the initial hour, followed by rapid, uniform decay in all organs including the kidney. The uptakes of both ethyl- and urea-14C in the brain were lowest among all organs examined. The RI-depositions in the fetal organs showed the same pattern of distribution as those in young female rats. The depositions also suggested free passage of ENU through the placenta. Subcellular distribution in the liver and kidney demonstrated a clear difference in the decay between ethyl- and urea-14C activities. While urea-14C activity showed a uniform exponential decrease in each subcellular fraction, the decay of ethyl-14C was delayed in all fractions except for the supernants, which decayed exponentially. In the subcellular fractions of 4 portions of the brain (cerebral cortex, white matter, cerebellum and brainstem), the same tendency could be found in time-course and distribution of ethyl-14C activity as in the liver and kidney, showing delayed clearance of the activity in all fractions except for the supernants. The uptakes of urea-14C also remained high in the nuclear fractions of each portion as long as 12 h after the injection, while decay was uniformly exponential in the other fractions. Uptakes in the region of the cerebral cortex were relatively higher among 4 portions, but the difference did not coincide with the common site of the tumor induced. The discrepancy between the distribution of 14C-ENU among organs and the subcellular fractions, and the preferential site for tumor induction by ENU was discussed. Significance of the subcellular accumulation of ethyl-14C in the liver and kidney on general metabolism was suggested. The importance of the reactions of alkyl radical with the cellular constituents other than nucleic acids and the role of the urea moiety of alkylnitrosoureas in carcinogenesis was also stressed.

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Accession: 005170577



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