Distinctive effects of mechlorethamine (NSC-762), cyclophosphamide (NSC-26271), and BCNU (NSC-409962) on transcription in Ehrlich cells.
Comparisons have been made between mechlorethamine, cyclophosphamide (CP), and BCNU as to the effects of chemotherapeutic drug levels on the transcription of RNA in vivo in Ehrlich cells. Mechlorethamine causes a dose-dependent depression in the synthesis of large Hn RNA transcripts in the nucleus and in the amount of large polysomal mRNA in the cytoplasm without apparent disturbance of polyadenylation and transport. Because of compensating increases in smaller Hn RNA and mRNA chains there is no inhibition of total RNA synthesis. CP seems to accelerate total Hn RNA and mRNA formation but inhibits polyadenylation. CP also produces an excess of short chains with only a minor depression of the synthesis of longer transcripts and messages. BCNU inhibits both RNA synthesis and polyadenylation but without disturbance of the size distribution of the polynucleotide chains. The results with mechlorethamine, in particular, are not easily explained on the basis of premature chain termination at the sites of DNA alkylation.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002330:Carmustine / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008466:Mechlorethamine / Q000494:pharmacology*; D051379:Mice; D009694:Nucleic Acid Precursors / Q000096:biosynthesis; D009713:Nucleotidyltransferases / Q000378:metabolism; D011061:Poly A / Q000096:biosynthesis; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*
D000477:Alkylating Agents; D009694:Nucleic Acid Precursors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011061:Poly A; D008466:Mechlorethamine; D000255:Adenosine Triphosphate; D003520:Cyclophosphamide; D009713:Nucleotidyltransferases; D002330:Carmustine