Mechanism of Killing Chinese Hamster Ovary Cells Heated in G 1 : Effects on DNA Synthesis and Blocking in G 2

Wong, Rosemary; Borrelli, Michael J.; Thompson, L. L.; Dewey, William C.

doi:10.2307/3577444

Cited by 25 publications

(7 citation statements)

References 4 publications

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“…In cells previously heated in G , for 10 min at 45.5"C, there was about a 12 hr delay in G I before they entered S phase. We found that the replicon initiation process was functional, the fork displacement rate had returned to a near normal rate, there was no increase in single-stranded regions in the replicating DNA, but there was still a similar delay in DNA chain elongation to complete inulticluster DNA molecules >120S in size [Wong et al, 1989a;Wong et al. 19931.…”

Section: Comparison With Heated Gi Cellsmentioning

confidence: 83%

“…To determine which of these four altered processes of DNA replication may be the critical step(s) in the induction process, we next investigated these same four processes in cells heated in G I , but now examined when they had entered S phase to replicate their DNA after a cell cycle block [Wong et al 1989a;Wong et al, 19931. Since heated G , cells do not die from the induction of chromosomal aberrations, any similarities or differences in these four S-phase altered processes between the 2 populations studied may help provide evidence as to which process is critical or required for the induction of aberrations.…”

Section: Comparison With Heated Gi Cellsmentioning

confidence: 99%

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Molecular mechanisms for the induction of chromosomal aberrations in CHO cells heated in S phase

Wong

Dewey

1993

Environ and Mol Mutagen

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Chromosomal aberrations are induced by heat only when Chinese hamster ovary cells are heated in S phase of the cell cycle. Studies on the hyperthermic inhibition of cellular DNA replication have indicated that four molecular aspects of DNA replication are affected after heating. New replicon initiation and DNA chain elongation are inhibited; the fork displacement rate is very sensitive to heat-inactivation; and finally, there is almost a two-fold increase in single-stranded regions in the replicating DNA after heating. From a comparison of these altered processes between S phase cells and heated G1 cells, which do not die from chromosomal aberrations, our current hypothesis involves 3 steps for the chromosomal aberration induction process. The first critical step is the persistent increase of single-stranded regions in the replicating DNA. Then, we hypothesize that the second step is the creation of transient double strand breaks (DSBs) induced at sites opposite these regions by endogenous endonucleases. Finally, the third step requires that improper repair of these DSBs occurs from either nonrepair or misrepair which then leads to the final chromosomal aberrations seen in the first mitosis after treatment. We believe that this 3 step induction process is common for any cytotoxic agent that induces chromosomal aberrations after DNA replication has been inhibited.

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Section: Comparison With Heated Gi Cellsmentioning

confidence: 83%

Section: Comparison With Heated Gi Cellsmentioning

confidence: 99%

Molecular mechanisms for the induction of chromosomal aberrations in CHO cells heated in S phase

Wong

Dewey

1993

Environ and Mol Mutagen

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“…Depending on the length of exposure and the cell line being heated, hyperthermia may perturb the cell cycle, leading to an accumulation of cells in S and G 2 phase after heat exposure [Coss, 1986;Wong et al, 1989]. Interestingly, lamin B appears to be synthesized only in S phase [Foisy and Bibor-Hardy, 1988;Jost and Johnson, 1981].…”

Section: Discussionmentioning

confidence: 99%

Heat-induced modulation of lamin B content in two different cell lines

1999

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Previous work in our laboratory indicates that the nuclear matrix protein lamin B is a "prompt" heat shock protein, which increases significantly when human U-1 melanoma and HeLa cells are exposed to 45.5 degrees C for 5-40 min. Using Western blotting, we found that the lamin B content in U-1 and HeLa cells increased to a greater extent during post-heat incubation at 37 degrees C than during the heat dose itself. When HeLa cells were heated at 45.5 degrees C for 30 min, and then incubated at 37 degrees C for up to 7 h, lamin B content was increased significantly (1.69-fold maximum increase at 3 h) compared to unincubated heated cells. Also, thermotolerant HeLa cells showed a greater increase (up to 1.72-fold) in lamin B content during subsequent heating compared to nontolerant cells. The increase in lamin B content in thermotolerant cells, or when heated cells were incubated at 37 degrees C, was also observed in U-1 cells. HeLa cells heated in the presence of glycerol (a heat protector) showed a 1.21-1.72-fold increase in lamin B content compared to cells heated for 10-30 min without glycerol. In contrast, lamin B content decreased 1.23-1.85-fold when cells were heated for 10-30 min in the presence of procaine (a heat sensitizer) compared to cells heated without procaine. These data suggest that lamin B may play an important role in the heat shock response, and that modulation of lamin B content by heat sensitizers or protectors may play a role in regulation of heat sensitivity.

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“…We found that the majority of cells were in the nonreplicative GI phase in this resistant period. Analysis of cell-cycle progression following a single -dose of hyperthermia revealed the blockage at GI, the most thermoresistant phase [28].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of hyperthermic toxicity by lonidarnine in the dunning R3327G rat prostatic adenocarcinoma

et al. 1994

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Hyperthermia alone or with radiation is used therapeutically for localized solid tumors. Clinical experience shows that sustained tumor temperature exceeding 45 degrees C damages normal tissue. Any agent that enhances the effects of hyperthermia at or below this temperature may have clinical relevance. Lonidamine and hyperthermia were tested on the Dunning R3327G rat prostatic adenocarcinoma. Using colony-formation assays, cytotoxic effects of each agent alone and in combination were quantified. Lonidamine to 100 micrograms/ml was not significantly toxic, but in combination, it enhanced cytotoxicity. Survival patterns after fractionated hyperthermia revealed a rapid development and decay of thermotolerance. Measurement of cell-cycle progression following a single dose of hyperthermia revealed a reduction of S-phase cells, and subsequent accumulation in G1 over 24 hours. Combination treatment of tumor-bearing rats significantly reduced tumor growth rate when compared with individual agents. These results suggest a potential use of lonidamine in hyperthermic therapy of prostate tumors.

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Mechanism of Killing Chinese Hamster Ovary Cells Heated in G 1 : Effects on DNA Synthesis and Blocking in G 2

Cited by 25 publications

References 4 publications

Molecular mechanisms for the induction of chromosomal aberrations in CHO cells heated in S phase

Molecular mechanisms for the induction of chromosomal aberrations in CHO cells heated in S phase

Heat-induced modulation of lamin B content in two different cell lines

Enhancement of hyperthermic toxicity by lonidarnine in the dunning R3327G rat prostatic adenocarcinoma

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