Mechanisms of the Radioprotective Effect of Cysteamine in Escherichia coli

Korystov, Yu. N.; Vexler, F B

doi:10.2307/3577125

Cited by 14 publications

(7 citation statements)

References 6 publications

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“…The close structural similarity between aminothiols (i.e., WR-1065) and polyamines @.e., spermidine and spermine) suggest that there may also be a similarity in the mechanism of action exhibited by these agents on cellular enzyme activities involved in DNA synthesis, cell-cycle progression and, possibly, repair. In particular, these results extend earlier observations (Hulsewede & Schulte- Frohlinde, 1986;Korystov & Vexler, 1988;Petin & Matrenina, 1981) of aminothiol interactions with cellular enzymes to now include the ability of WR-1065 to affect the nuclear enzyme topoisomerase II.…”

Section: Wr-io65 Effects On the Activities Of Topoisomerases I And Iisupporting

confidence: 87%

“…Radiation protection studies performed on DNA repair-deficient organisms strongly support the suggestion that endogenous enzyme systems are dominant parameters which can influence the magnitude of aminothiol-mediated protection. While cysteamine was found to be an effective protective agent in wild-type E. coli, it was not protective in bacterial strains with defects in the rec system (Hulsewede & Schulte- Frohlinde, 1986;Korystov & Vexler, 1988). E. coli mutants deficient in POL I or UV endonucleases were also not amenable to protection by cysteamine (Korystov & Vexler, 1988).…”

Section: Wr-io65 Effects On the Activities Of Topoisomerases I And Iimentioning

confidence: 99%

“…While cysteamine was found to be an effective protective agent in wild-type E. coli, it was not protective in bacterial strains with defects in the rec system (Hulsewede & Schulte- Frohlinde, 1986;Korystov & Vexler, 1988). E. coli mutants deficient in POL I or UV endonucleases were also not amenable to protection by cysteamine (Korystov & Vexler, 1988). Likewise, x-ray repairdeficient rad mutants of Saccharomyces cerevisia were reported to be unprotectable by cysteamine (Petin & Matrenina, 1981).…”

Section: Wr-io65 Effects On the Activities Of Topoisomerases I And Iimentioning

confidence: 99%

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Inhibition of topoisomerase II activity in CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

Grdina¹,

Constantinou²,

Shigematsu³

1993

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The aminothiol2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of the clinically studied radioprotective agent S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721). WR-1065 is an effective radiation protector and antimutagenic agent when it is administered 30 min prior to radiation exposure to Chinese hamster ovary K1 cells (i.e., a dose modification factor of 1.4) at a concentration of 4 mM. Under these exposure conditions, topoisomerase (topo) I and I1 activities and associated protein contents were measured in the K1 cell line using a DNA relaxation assay and immunoblotting. WR-1065 was ineffective in modifying top0 I activity, but it did reduce top0 11 activity by 50 percent. The magnitude of top0 I1 protein content, however, was not affected by these exposure conditions. Cell-cycle effects were monitored by the method of flow cytometry. Exposure of cells to 4 mM of WR-1065 for a period of up to 3 h resulted in a buildup of cells in the G2 compartment. However, in contrast to top0 I1 inhibitors used in chemotherapy, WR-1065 is an effective radioprotector agent capable of protecting against both radiation-induced cell lethality and mutagenesis. One of several mechanisms of radiation protection attributed to aminothiol compounds such as WR-1065 has been their ability to affect endogenous enzymatic reactions involved in DNA synthesis, repair, and cell-cycle progression. These results are consistent with such a proposed mechanism and demonstrate in particular a modifying effect by 2-[(aminopropyl)arnino]ethanethiol on type I1 topoisomerase, which is involved in DNA synthesis.

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Section: Wr-io65 Effects On the Activities Of Topoisomerases I And Iisupporting

confidence: 87%

Section: Wr-io65 Effects On the Activities Of Topoisomerases I And Iimentioning

confidence: 99%

Section: Wr-io65 Effects On the Activities Of Topoisomerases I And Iimentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of topoisomerase II activity in CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

Grdina¹,

Constantinou²,

Shigematsu³

1993

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“…Thiols also react avidly with oxygen, reducing the rate of formation of peroxyl radicals. Cysteamine lowers indirect radiation effects by scavenging hydroxyl (400).…”

Section: Antioxidativementioning

confidence: 99%

Physiological actions of taurine

Huxtable

1992

Physiological Reviews

2,387

1,625

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TABLE 1. Some biological actions of taurine Action References Action References Cardiovascular system Antiarrhythmic Positive inotropy at low calcium Negative inotropy at high calcium Potentiation of digitalis inotropy Antagonism of calcium paradox Hypotensive (central and peripheral action) Retardation of lesion development in calcium overload cardiomyopathy Increased resistance of platelets to aggregation

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“…Radiation protection studies performed on DNA repair-deficient organisms strongly support the suggestion that endogenous repair systems are dominant parameters which can influence the magnitude of aminothiol-mediated protection. While cysteamine was found to be an effective protective agent in wild-type E. coli, it was not protective in bacterial strains with defects in the rec system (32,33). E. coli mutants deficient in poL I or UV endonucleases were also not amenable to protection by cysteamine (33).…”

Section: Introductionmentioning

confidence: 98%

Inhibition of topoisomerase II activity in repair-proficient CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

Grdina¹,

Constantinou²,

Shigematsu³

1992

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The aminothiol 2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of the clinically studied radioprotective agent S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721). WR-1065 is an effective radiation protector under in vitro conditions when it is administered 30 min prior to radiation exposure at a concentration of 4 mM to repair-proficient Chinese hamster ovary K1 cells (i.e., a dose modifcafion factor of 1.4). In contrast, the DNA double-strand break, repair-deficient Chinese hamster ovary xrs-5 cell line is not protected under these conditions (i.e., a dose modification factor of i.0). Topoisomerase (topo) I and II activities and protein contents were measured in both K1 and xrs-5 cell lines and were found to be similar in magnitude. Neither exposure to radiation, to WR-1065, or to both affected these variables in xrs-5 cells. WR-1065 was effective, however, in reducing topo II activity by a factor of 2 in the repair-proficient K1 cell line. Topo II protein content, however, was not affected by these exposure conditions. One of several mechanisms of radiation protection attributed to aminothiol compounds has been their ability to affect enzymatic reactions involved in DNA synthesis, repair, and cell cycle progression. These results demonstrate a modifying effect by 2-[(aminopropyl)amino]ethanethiol on a specific nuclear enzyme (i.e., type II topoisomerase), which is involved in DNA synthesis. These results also suggest that differences do exist between the topo II enzymes isolated from the paren: repair-proficient K1 and the DNA double-strand break, repair-deficient xrs-5 mutant cell lines.

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Mechanisms of the Radioprotective Effect of Cysteamine in Escherichia coli

Cited by 14 publications

References 6 publications

Inhibition of topoisomerase II activity in CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

Inhibition of topoisomerase II activity in CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

Physiological actions of taurine

Inhibition of topoisomerase II activity in repair-proficient CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

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