Cellular responses to antimetabolite anticancer agents: cytostasis versus cytotoxicity.
Thymineless death is an important cytotoxic response to several classes of antimetabolite agents used in the treatment of patients with carcinomas and hematopoeitic malignancies. Cell death induced by lack of dThd results in the formation of DNA nucleosomal ladders, and hence would be defined as a form of apoptosis. Although drug resistance to these agents has been extensively studied, relatively little attention has been focused on events downstream of dTTP depletion that determine the ultimate fate of the cancer cell. In this article we review some of the emerging data that suggests the role of p53 in determining whether the cellular response to dThd deprivation is cytostasis or cytotoxicity (apoptosis).
Houghton
J A
JA
Department of Molecular Pharmacology St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Houghton
P J
PJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D003854:Deoxyribonucleotides / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016158:Genes, p53; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013941:Thymine / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D003854:Deoxyribonucleotides; D004791:Enzyme Inhibitors; D013940:Thymidylate Synthase; D013941:Thymine