Hypoxic Radiosensitizers and Cellular Respiration

Re, Duran; Je, Biaglow; Rm, Sutherland

doi:10.1259/0007-1285-49-582-567

Cited by 22 publications

(3 citation statements)

References 3 publications

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“…A related nitroimidazole, metronidazole, inhibits cellular 02 utilization (Biaglow et al, 1974;Durand et al, 1976) which could be associated with less energy and heat production. At 06 mg/g body wt, a decrease in heart rate of ,35% and a decrease in body temperature of almost 6°C in unanaesthetized C3H mice has been reported (Haynes & Inch, 1976).…”

Section: Resultsmentioning

confidence: 99%

Peripheral electrophysiological parameters in mice treated with misonidazole

Burg¹,

Conroy²,

Passalacqua³

1979

Br J Cancer

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Summary.-The clinical use of the radiosensitizer misonidazole may be limited by the incidence of peripheral neuropathy reported following total doses in excess of 18 g. A recent report noted a decrease in nerve conduction velocity following a single i.p. injection of 1 mg/g misonidazole to mice. The present study was unable to confirm such changes when nerve conduction velocity measurements were made in situ or in isolated sural, tibial or median nerves of mice. Other electrophysiological parameters such as threshold, strength-duration curves, refractory time or the ability to carry high-frequency stimulation also showed no change. However, it was noted that a single administration of the radio-sensitizer produced a marked decrease in body temperature which persisted for at least 2 h after the elimination of the drug from the blood serum. The physiological response of reduction of body temperature may protect the mouse against the effect of the toxic chemical species involved in the induction of neurotoxicity.

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Section: Resultsmentioning

confidence: 99%

Peripheral electrophysiological parameters in mice treated with misonidazole

Burg¹,

Conroy²,

Passalacqua³

1979

Br J Cancer

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“…Although there may be little or no net nitroreduction in aerobic systems because of reaction (2), there may be a stimulation of respiration, a feature which Biaglow, Durand, Sutherland, et al (25)(26)(27)(28)(29) recognized may be important in the potentially widespread use of nitroaryl compounds in cancer therapy (31)(32)(33)(34). The oxygen tension in tumor cells may control the radiotherapeutic response, and nitro compounds (and other oxidants) are able to sensitize hypoxic cells to radiation, with a negligible effect on the radiosensitivity of well-oxygenated tissues.…”

Section: Introductionmentioning

confidence: 99%

Some reactions and properties of nitro radical-anions important in biology and medicine.

Wardman¹

1985

Environ Health Perspect

164

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Nitroaromatic compounds, ArNO2 have widespread actual or potential use in medicine and cancer therapy. There is direct proof that free-radical metabolites are involved in many applications, and an appreciation of the conceptual basis for their therapeutic differential; however, an understanding of the detailed mechanisms involved is lacking. Redox properties control most biological responses of nitro compounds, and the characteristics of the one-electron couple: ArNO2/ArNO2- are detailed. The "futile metabolism" of nitroaryl compounds characteristic of most aerobic nitroreductase systems reflects competition between natural radical-decay pathways and a one-electron transfer reaction to yield superoxide ion, O2-. Prototropic properties control the rate of radical decay, and redox properties control the rate of electron transfer to O2 or other acceptors. There are clear parallels in the chemistry of ArNO2- and O2-. While nitro radicals have frequently been invoked as damaging species, they are very unreactive (except as simple reductants). It seems likely that reductive metabolism of nitroaryl compounds, although generally involving nitro radical-anions as obligate intermediates (and this is required for therapeutic selectivity towards anaerobes), results in biological damage via reductive metabolites of higher reduction order than the one-electron product.

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“…(25)(26)(27)(28)(29) recognized may be important in the potentially widespread use of nitroaryl compounds in cancer therapy (31)(32)(33)(34). The oxygen tension in tumor cells may control the radiotherapeutic response, and nitro compounds (and other oxidants) are able to sensitize hypoxic cells to radiation, with a negligible effect on the radiosensitivity of well-oxygenated tissues.…”

Section: Introductionmentioning

confidence: 99%

Some Reactions and Properties of Nitro Radical-Anions Important in Biology and Medicine

Wardman¹

1985

Environmental Health Perspectives

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Nitroaromatic compounds, ArNO2 have widespread actual or potential use in medicine and cancer therapy. There is direct proof that free-radical metabolites are involved in many applications, and an appreciation of the conceptual basis for their therapeutic differential; however, an understanding of the detailed mechanisms involved is lacking. Redox properties control most biological responses of nitro compounds, and the characteristics of the one-electron couple: ArNO2/ArNO2 are detailed. The "futile metabolism" of nitroaryl compounds characteristic of most aerobic nitroreductase systems reflects competitioq between natural radical-decay pathways and a one-electron transfer reaction to yield superoxide ion, 02-Prototropic properties control the rate of radical decay, and redox properties control the rate Qf electron transfer to 02 or other acceptors. There are clear parallels in the chemistry of ArNO2 and°2-While nitro radicals have frequently been invoked as damaging species, they are very unreactive (except as simple reductants). It seems likely that reductive metabolism of nitroaryl compounds, although generally involving nitro radical-anions as obligate intermediates (and this is required for therapeutic selectivity towards anaerobes), results in biological damage via reductive metabolites of higher reduction order than the one-electron product.

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Hypoxic Radiosensitizers and Cellular Respiration

Cited by 22 publications

References 3 publications

Peripheral electrophysiological parameters in mice treated with misonidazole

Peripheral electrophysiological parameters in mice treated with misonidazole

Some reactions and properties of nitro radical-anions important in biology and medicine.

Some Reactions and Properties of Nitro Radical-Anions Important in Biology and Medicine

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