Cell killing, chromosomal aberrations, and division delay as thermal sensitivity is modified during the cell cycle.
Synchronous Chinese hamster ovary cells were treated in G1 or S phase with cycloheximide or procaine hydrochloride before and during heating at 43 degrees C. Cycloheximide and procaine apparently act by different mechanisms, with cycloheximide inhibiting protein synthesis and procaine hydrochloride supposedly affecting cellular membranes. Both agents, however, modify the heat damage expressed as chromosomal aberrations, cell killing, or division delay. Furthermore, the approximately twofold protection with cycloheximide treatment or twofold sensitization with procaine treatment is the same for the three end points and for heating during either G1 or S phase. However, heat induces chromosomal aberrations observed in metaphase when cells are heated in S phase but not when they are heated in G1. Finally, for the three end points, the activation energy is about 140-152 kcal/mol. Therefore, heat may induce a common intracellular phenomenon involving protein denaturation or aggregation that is responsible for the damage observed by division delay, chromosomal aberrations, and cell-killing. There are great differences in division delay induced during the cell cycle by heat or radiation. Division delay is the same when cells are heated in the relatively heat-resistant G1 phase or the relatively heat-sensitive S phase, with about 15 min of delay for 1 min of heating at 43 degrees C. This contrasts with the increase in division delay observed when cells are irradiated in the relatively radioresistant S phase compared with the relatively radiosensitive G1 phase. Quantitatively, division delay for a treatment that reduces survival to about 0.1 is 15 or 25 h for heating in S or G1, respectively, compared with only 6 or 1.5 h for irradiation in S or G1, respectively.
Dewey
W C
WC
Radiation Oncology Research Laboratory, University of California, San Francisco 94143-0806.
Li
X L
XL
Wong
R S
RS
D000064:Acclimatization / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002869:Chromosome Aberrations / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology*; D006358:Hot Temperature; D011343:Procaine / Q000494:pharmacology*; D013997:Time Factors
D011343:Procaine; D003513:Cycloheximide