Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 19 69

Combined effect of twenty-one central nervous system depressants with several antitumor agents was studied in the in vitro and in vivo experimental systems, using rat ascites hepatoma call lines, AH13 and AH44, sensitive and insensitive to alkylating agents, respectively. Reserpine remarkably enhanced the cytotoxic effect of 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2) both on AH13 and AH44 cells. In the in vivo combined experiments, reserpine also synergistically enhanced the life-prolonging effect of CAP-2 on AH13-bearing rats and, although CAP-2 was not potent on the prolongation of life span of AH44-bearing rats and reserpine was also ineffective at the doses examined, the life span of tumor-bearing rats receiving the combined administration was apparently prolonged compared with control groups. Thus, there was a parallelism between in vitro and in vivo experiments. These findings suggested that the antitumor-enhancing effect of reserpine might be due to the direct action on the tumor cells, and a possible mechanism that reserpine inhibited the DNA damage-repairing activity of the cells was contradictory. Other mechanisms are also discussed.
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PMID:Combination antitumor effect with central nervous system depressants on rat ascites hepatomas. 738 Jan 36