In vivo binding of N-nitrosopyrrolidine and N-nitrosohexamethyleneimine to non-purine sites on rat liver DNA.
Liver DNA and RNA were isolated from rats treated with the liver carcinogens N-nitrosopyrrolidine (NPYR) and N-nitrosohexamethyleneimine (NHX). After hydrolysis in 70% perchloric acid (100 degrees C, 1.0 h), 70% of the radioactivity in both the DNA and RNA hydrolysates chromatographed as a single peak. The material from both hydrolysates had comparable Rf values on cation exchange and Sephadex G-10 chromatography. Subsequent experiments indicated this material was volatile. After depurination (0.1 M HCl) of the DNA from NPYR- and NHX-treated rats, Sephadex G-10 chromatography separated only a single radioactive peak which co-eluted with the apurinic acid at the void volume. The material which comprised this peak was not volatile. After dialysis of the same 0.1 M HCl hydrolysate from NHX-treated rats, 98% of the radioactivity remained attached to the apurinic acid. These 2 cyclic nitrosamines appear to produce alkylating species that: (1) are capable of extensive, if not exclusive, phosphotriester formation; or (2) have 2 active sites that cross-link to keep purines attached to apurinic acid after 0.1 M HCl hydrolysis.
D000818:Animals; D001080:Apurinic Acid / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009242:N-Nitrosopyrrolidine / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D002273:Carcinogens; D009602:Nitrosamines; D011687:Purines; D014316:Tritium; D001080:Apurinic Acid; D012313:RNA; D004247:DNA; C002742:N-nitrosoperhydroazepine; D009242:N-Nitrosopyrrolidine