Summary
The stability of the binding of radioactive metabolites from the carcinogen N-hydroxy-N-2-fluorenylacetamide to macromolecular elements in rat liver was studied after a single dose of compound and after 2 and 10 weeks of dietary intake of the labeled carcinogen. After a single dose the label of carcinogen bound to DNA decreased in two discrete steps. After the initial peak at 24 hours, the bound label decreased with a half-life of 10 hours, then declined with a half-life of about 33 hours between the 4th and 12th day by when virtually all the label was lost. In cytoplasmic fractions the label decreased to zero in 24 days. The persistence of label introduced into DNA with tritiated thymidine was found to be relatively uniform between Day 6 and Day 72 after a single dose.
The initial peak value of carcinogen bound to DNA, the microsomal fraction, and the soluble fraction, was higher after continuous intake of 2 weeks than after 10 weeks. On the DNA the maximum binding corresponded to about 11,000 nucleotide units for 1 molecule of carcinogen. The rate of decrease was similar for the 2-week and the 10-week groups for the first few days after cessation of labeled carcinogen intake. Subsequently the decline of bound activity was slower in the 10-week group than in the 2-week group. With this type of carcinogen, measurement of the interaction between agent and cellular elements performed after feeding of the compound for a time period eventuating in cancer is more relevant to an understanding of the process than is the measurement performed after single dosing.
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