L-homoserine hydroxamic acid as an antitumor agent.
This report confirms the potent mutagenic and antitumor activity of L-homoserine hydroxamic acid in both in vitro and in vivo test systems. Its mutagenic potential is evident in the developing tadpoles of Xenopus laevis eggs exposed to the compound. Cytotoxic effects are demonstrated against human leukemia and melanoma cell lines proliferating in tissue culture and against xenografts of human breast cancer and sarcoma growing in nude mice. We propose that the mutagenic and antitumor activity are mediated through hydroxylamine, which is released from its stable carrier amino acid, homoserine, consequent to a reduction in pH occurring at the cellular level. The cytotoxic effects of L-homoserine hydroxamic acid are more intense than those of the D-isomer and are more evident in neoplastic than in normal cell lines.
Natelson
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University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, Knoxville 37901.
Pantazis
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P
Natelson
E A
EA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D005260:Female; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D007938:Leukemia / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000473:pathology; D009153:Mutagens / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D009865:Oocytes / Q000187:drug effects; D012509:Sarcoma / Q000473:pathology; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D000970:Antineoplastic Agents; D009153:Mutagens; C090905:homoserine hydroxamic acid; D006714:Homoserine; D004247:DNA