Suggestive evidence for relationship between sensitivity and repair capability in rat ascites hepatoma cells treated with the antitumor agent, 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide.
Antitumor activity of 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2) was studied in vivo and in vitro, using various rat ascites hepatoma cell lines. Among eight ascites hepatoma cell lines, AH-13 was extremely sensitive both to in vivo antitumor and to in vitro lethal action of the agent, whereas AH-44 was resistant in both cases. The sensitivity of ascites hepatoma cell lines to CAP-2, nitrogen mustard N-oxide, 4-nitroquinoline 1-oxide, and ultraviolet ray in vitro was widely different but their relative sensitivities were very similar against these agents. For all the agents, AH-13 was inactivated very rapidly and AH-109A moderately, whereas AH-44 was relatively resistant. These results indicate that the sensitivity of the cells to CAP-2 may be closely related to their repair-capability of damaged DNA. Similar experiments using various DNA repair-deficient mutants of Escherichia coli B strain demonstrated that the repair-deficient mutants were several times more sensitive to CAP-2 than the wild type strain. From these results, it may be concluded that CAP-2 induces DNA lesions repairable by the same repair mechanisms that work on pyrimidine dimers.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D002460:Cell Line; D004260:DNA Repair / Q000187:drug effects; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009154:Mutation; D009374:Neoplasms, Experimental; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
D004269:DNA, Bacterial; D009588:Nitrogen Mustard Compounds; D010880:Piperidines; D015112:4-Nitroquinoline-1-oxide