H. Gutmann, U. Seal, C. Irving
Aug 1, 1960
Citations
0
Influential Citations
15
Citations
Quality indicators
Journal
Cancer research
Abstract
Homogenates of six rat tissues metabolized the o -amidofluorenol, N-(1-hydroxy-2-fluorenyl)acetamide, as judged by the disappearance of the phenolic hydroxyl group of the compound from the incubation systems. By the same criterion, N-(7-hydroxy-2-fluorenyl)acetamide was resistant to metabolic attack. The deacylation of N-(1-hydroxy-2-fluorenyl)acetamide, N-(7-hydroxy-2-fluorenyl)acetamide, N-2-fluorenylbutyramide, and N-2-fluorenylacetamide by twelve rat tissues was examined with the use of spectrophotometric technics and radioactive tracer methods. Only N-(1-hydroxy-2-fluorenyl)acetamide was deacetylated by all tissues. The action of 0.1 m potassium fluoride upon deacetylation of N-(1-hydroxy-2-fluorenyl)acetamide-1-C14 and upon protein labeling by the radioactivity of N-2-fluorenylacetamide-9-C14 was examined in rat liver homogenates; 0.1 m potassium fluoride inhibited deacetylation as well as protein labeling. It was confirmed in separate experiments that fluoride under these conditions enhanced hydroxylation as previously described. The data support a mechanism of protein binding of the carcinogen previously suggested on the basis of in vitro evidence. This mechanism involves o -hydroxylation of N-2-fluorenylacetamide followed by deacetylation and subsequent oxidation of the resulting o -aminophenol to the o -quinoneimine which in turn may combine with protein. The role of the inhibition of protein synthesis by dl-ethionine upon the binding of N-2-fluorenylacetamide-9-C14 was tested. No effect of this antimetabolite upon binding was observed.