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EFFECTS OF HYPERTHERMIA ON DNA POLYM...

SPIRO, IRA JAY.

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EFFECTS OF HYPERTHERMIA ON DNA POLYMERASE ACTIVITIES AND SURVIVAL OF CHINESE HAMSTER OVARY CELLS.

Record Type:	Electronic resources : Monograph/item
Title/Author:	EFFECTS OF HYPERTHERMIA ON DNA POLYMERASE ACTIVITIES AND SURVIVAL OF CHINESE HAMSTER OVARY CELLS./
Author:	SPIRO, IRA JAY.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 1981,
Description:	183 p.
Notes:	Source: Dissertations Abstracts International, Volume: 42-07, Section: B.
Contained By:	Dissertations Abstracts International42-07B.
Subject:	Radiology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8119732
ISBN:	9798204517165

EFFECTS OF HYPERTHERMIA ON DNA POLYMERASE ACTIVITIES AND SURVIVAL OF CHINESE HAMSTER OVARY CELLS.
SPIRO, IRA JAY.

EFFECTS OF HYPERTHERMIA ON DNA POLYMERASE ACTIVITIES AND SURVIVAL OF CHINESE HAMSTER OVARY CELLS. - Ann Arbor : ProQuest Dissertations & Theses, 1981 - 183 p.

Source: Dissertations Abstracts International, Volume: 42-07, Section: B.

Thesis (Ph.D.)--Colorado State University, 1981.

This item must not be sold to any third party vendors.

A whole cell DNA polymerase assay technique was characterized in CHO cells. The amount of thymidine triphosphate incorporated by DNA polymerase-(beta) (pol-(beta)) was observed to increase linearly (a)for incubation times from 5-11 min and (b)with increasing cell number (10('5) - 10('6)). Also, this assay system was used to show the cell cycle distributions of both pol-(alpha) and pol-(beta). Pol-(alpha) was shown to increase over twofold during a 2 hr span in mid-S phase, while pol-(beta) increased linearly during the cell cycle. The assay system described above was used to show that the loss of pol-(beta) activity in heated cells closely correlated with hyperthermic cell killing and hyperthermic radiosensitization. For example, a plateau in the pol-(beta) inactivation curve developed within several hr after heating cells at temperatures (LESSTHEQ) 42.5(DEGREES)C. This same phenomenon is observed for hyperthermic cell killing. Additionally, procaine-HCl (7 mM) enhanced the loss of pol-(beta) activity when whole cells were heated at 42.2(DEGREES)C. An identical concentration of procaine-HCl also will markedly enhance heat-induced cell killing. Also, the return of pol-(beta) activity at 37(DEGREES)C following a heat shock (10 min, 45.5(DEGREES)C) correlated with the increase in cell survival when the same heat shock and an x-ray treatment (4 Gy) were separated by corresponding amounts of time at 37(DEGREES)C. Furthermore, the loss of pol-(beta) activity, measured as a function of increasing heat dose, correlated with the heat-induced depression of x-ray-induced unscheduled DNA synthesis. These last two findings indicate that the heat-induced enhancement of x-ray killing may result from heat-induced reduction of pol-(beta) activity. Finally, heat studies with isolated pol-(beta) indicated that the reduction of pol-(beta) in heated cells is due to direct thermal denaturation although this loss can be enhanced indirectly in whole cells by Procaine-HCl. Survival studies with CHO cells showed that thermal tolerance (TT, i.e., a decrease in the rate of cell killing) which developed during chronic heating (treatment times (GREATERTHEQ) 1 hr) or after acute heating (treatment times < 1 hr) involves similar mechanisms. For example, cells that expressed TT during a 6-14 hr chronic heat treatment at 41.5(DEGREES)C or 42(DEGREES)C also expressed TT to a subsequent acute treatment at 45.5(DEGREES)C. Also, cells heated acutely for 10 min at 45.5(DEGREES)C and incubated at 37(DEGREES)C for 12 hr displayed TT to both 45.5(DEGREES)C acute and 42(DEGREES)C chronic hyperthermia. Finally, TT developed between fractionated acute and fractionated chronic heat treatments. These results indicate that when cells are tolerant to acute heating they are also tolerant to chronic heating and that the reverse is also true.

ISBN: 9798204517165Subjects--Topical Terms:

894545
Radiology.

EFFECTS OF HYPERTHERMIA ON DNA POLYMERASE ACTIVITIES AND SURVIVAL OF CHINESE HAMSTER OVARY CELLS.
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100 1 $a SPIRO, IRA JAY. $3 3763665
245 1 0 $a EFFECTS OF HYPERTHERMIA ON DNA POLYMERASE ACTIVITIES AND SURVIVAL OF CHINESE HAMSTER OVARY CELLS.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 1981
300 $a 183 p.
500 $a Source: Dissertations Abstracts International, Volume: 42-07, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
502 $a Thesis (Ph.D.)--Colorado State University, 1981.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a A whole cell DNA polymerase assay technique was characterized in CHO cells. The amount of thymidine triphosphate incorporated by DNA polymerase-(beta) (pol-(beta)) was observed to increase linearly (a)for incubation times from 5-11 min and (b)with increasing cell number (10('5) - 10('6)). Also, this assay system was used to show the cell cycle distributions of both pol-(alpha) and pol-(beta). Pol-(alpha) was shown to increase over twofold during a 2 hr span in mid-S phase, while pol-(beta) increased linearly during the cell cycle. The assay system described above was used to show that the loss of pol-(beta) activity in heated cells closely correlated with hyperthermic cell killing and hyperthermic radiosensitization. For example, a plateau in the pol-(beta) inactivation curve developed within several hr after heating cells at temperatures (LESSTHEQ) 42.5(DEGREES)C. This same phenomenon is observed for hyperthermic cell killing. Additionally, procaine-HCl (7 mM) enhanced the loss of pol-(beta) activity when whole cells were heated at 42.2(DEGREES)C. An identical concentration of procaine-HCl also will markedly enhance heat-induced cell killing. Also, the return of pol-(beta) activity at 37(DEGREES)C following a heat shock (10 min, 45.5(DEGREES)C) correlated with the increase in cell survival when the same heat shock and an x-ray treatment (4 Gy) were separated by corresponding amounts of time at 37(DEGREES)C. Furthermore, the loss of pol-(beta) activity, measured as a function of increasing heat dose, correlated with the heat-induced depression of x-ray-induced unscheduled DNA synthesis. These last two findings indicate that the heat-induced enhancement of x-ray killing may result from heat-induced reduction of pol-(beta) activity. Finally, heat studies with isolated pol-(beta) indicated that the reduction of pol-(beta) in heated cells is due to direct thermal denaturation although this loss can be enhanced indirectly in whole cells by Procaine-HCl. Survival studies with CHO cells showed that thermal tolerance (TT, i.e., a decrease in the rate of cell killing) which developed during chronic heating (treatment times (GREATERTHEQ) 1 hr) or after acute heating (treatment times < 1 hr) involves similar mechanisms. For example, cells that expressed TT during a 6-14 hr chronic heat treatment at 41.5(DEGREES)C or 42(DEGREES)C also expressed TT to a subsequent acute treatment at 45.5(DEGREES)C. Also, cells heated acutely for 10 min at 45.5(DEGREES)C and incubated at 37(DEGREES)C for 12 hr displayed TT to both 45.5(DEGREES)C acute and 42(DEGREES)C chronic hyperthermia. Finally, TT developed between fractionated acute and fractionated chronic heat treatments. These results indicate that when cells are tolerant to acute heating they are also tolerant to chronic heating and that the reverse is also true.
590 $a School code: 0053.
650 4 $a Radiology. $3 894545
650 4 $a Medical imaging. $3 3172799
690 $a 0574
710 2 $a Colorado State University. $3 675646
773 0 $t Dissertations Abstracts International $g 42-07B.
790 $a 0053
791 $a Ph.D.
792 $a 1981
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8119732