Comparative carcinogenicities and reactivities of N-myristoyloxy-N-acetyl-2-aminofluorene and its 7-iodo derivative.
Earlier studies showed that N-acetyl-2-aminofluorene (AAF) is much more carcinogenic than N-acetyl-2-amino-7-iodofluorene (AAIF). Subsequently it was found that substitution of C-8 of guanine bases in DNA with AAF residues resulted in displacement of the guanine bases outside the DNA helix. This did not occur after similar substitution with AAIF residues. As one approach to assessing the possible importance of this gross conformational difference to the carcinogenicity of AAF, the carcinogenic activities of two electrophilic esters, N-myristoyloxy-AAF and its 7-iodo derivative, were compared by s.c. injection into male Fischer rats. On injection of a total of 64 mumol, each ester induced a high incidence of sarcomas, and the latent periods were similar. N-Myristoyloxy-AAIF was solvolyzed in aqueous media at about one-half the rate of N-myristoyloxy-AAF, and it was less than 10% as reactive with native DNA as N-myristoyloxy-AAF. N-Myristoyloxy-AAF and N-myristoyloxy-AAIF were each less reactive than the corresponding acetoxy derivatives. These data suggest that the low carcinogenicity of AAIF as compared to that of AAF may not be associated with the conformations of their adducts in the DNA. This difference in carcinogenicity may be related to differences in the rates of metabolic activation and inactivation of these two amides.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D000818:Animals; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D008297:Male; D051381:Rats; D012513:Sarcoma, Experimental / Q000139:chemically induced
D002273:Carcinogens; C025804:N-myristoyloxy-N-acetyl-2-aminofluorene; C032018:N-myristoyloxy-N-acetyl-2-amino-7-iodofluorene; D004247:DNA; D015073:2-Acetylaminofluorene