The molecular basis of drug-induced G2 arrest in mammalian cells.
The purpose of this review was to focus mainly on the molecular events related to the progression of cells through the G2 period to examine the cause for G2-arrest in mammalian cells after exposure to various anticancer drugs. With few exceptions, most of the eukaryotic cells exhibit a G2 period in their life cycles. The G2 period, which separates S phase from mitosis, represents the time necessary for the synthesis of the various components related to the condensation of chromosomes, assembly of the mitotic spindle, and cytokinesis. Continued synthesis of RNA and protein is necessary for the successful completion of G2 and the initiation of mitosis. Inhibition of RNA and protein synthesis, replacement of phenylalanine by its analog paraversible G2 arrest in cultured cells. Exposure of cells to certain antineoplastic drugs also blocks cells preferentially in G2. This irreversible drug-induced G2 arrest is associated with extensive chromosome damage. The G2-arrested cells were found to be deficient in certain proteins that may be specific for the G2-mitotic transition. These mitotic or chromosome condensation factors synthesized during the G2 period, reach their maximum levels at mitosis. A preliminary characterization of the chromosome condensation factor revealed that it is a heat labile, Ca2+-sensitive, nondialyzable protein with a sedimentation value of 4-5S.
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002459:Cell Fusion; D002875:Chromosomes / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004317:Doxorubicin / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000166:cytology; D007399:Interphase / Q000187:drug effects* / Q000528:radiation effects; D008938:Mitosis / Q000187:drug effects; D010222:Parainfluenza Virus 1, Human / Q000528:radiation effects; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D014466:Ultraviolet Rays; D014965:X-Rays; D009353:Zinostatin / Q000494:pharmacology; D010135:p-Fluorophenylalanine / Q000494:pharmacology
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D010135:p-Fluorophenylalanine; D012313:RNA; D003994:Bucladesine; D004317:Doxorubicin; D004247:DNA; D009353:Zinostatin; D003513:Cycloheximide; D000242:Cyclic AMP