Inhibition of DNA Repair Replication by DNA Binding Drugs Which Sensitize Cells to Alkylating Agents and X-Rays

Gaudin, D.; Gregg, Robert; Yielding, K. Lemone

doi:10.3181/00379727-141-36818

Cited by 15 publications

(4 citation statements)

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“…(2) a repair process confined to replicative synthesis (Cleaver and Thomas 1969, Domon and Rauth 1969, Fabre 1972, Gaudin et al 1972); or (3) RNA and protein but not DNA synthesis (uk and Swietlifiska 1973), or vice versa (Mitznegg et al 1971). T'so and Lu (1964) structural changes of the DNA molecule which result in the stability of DNA, and through this the substrate for repair enzymes becomes changed and their reactivities affected.…”

Section: Introductionmentioning

confidence: 98%

Differential Modification of Oxic and Anoxic Components of Radiation Damage inBacillus MegateriumSpores by Caffeine

Kesavan¹,

Powers²

1985

International Journal of Radiation Biology and Related Studies

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Studies were carried out on the effect of caffeine on the X-irradiation sensitivity of B. megaterium spores with the following results: Caffeine exerts a concentration-dependent modifying action on oxygen-dependent components of X-ray-induced damage in B. megaterium spore suspensions causing an 'over-O2 effect' at about 1 X 10(-4) mol dm-3, and as the concentration is increased to 1 X 10(-3) mol dm-3 or above, a small but consistent protection is seen. In the absence of O2, at a wide range of concentrations (8.5 X 10(-5) to 1 X 10(-1) mol dm-3), caffeine enhances the inactivation constant, k, from 1.17 to about 1.50 kGy-1. Both ethanol and t-butanol (5 X 10(-2) mol dm-3) remove the 'over O2-effect' produced by 1.10(-4) mol dm-3 caffeine in O2; such an effect, however, is not accompanied by reduction in the H2O2 concentrations in the spore suspensions. Ethanol prevents caffeine-induced anoxic sensitization, as well as H2O2 buildup. t-BuOH has no influence on either the low dose part of the log fraction survival curve or on the H2O2 yield in the spore suspensions. Caffeine reacts with radiation-induced eaq and .OH with rate constants of 1.5 X 10(10) and 6.9 X 10(9) dm3 mol-1s-1, respectively.

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Section: Introductionmentioning

confidence: 98%

Differential Modification of Oxic and Anoxic Components of Radiation Damage inBacillus MegateriumSpores by Caffeine

Kesavan¹,

Powers²

1985

International Journal of Radiation Biology and Related Studies

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“…Phosphoramide mustard is known to destroy rapidly dividing cells by covalently binding to DNA, inducing DNA-DNA, DNA-protein cross links, and DNA double strand breaks (DSBs) [16][17][18]. Upon DSB induction, cells activate their DNA damage response (DDR) that comprises cell cycle arrest, DNA damage repair, and subsequent cell cycle resumption [19][20][21][22]. Phosphorylation of the histone H2AX (γ H2AX) at Serine 19 is an early event in the DDR, resulting in recruitment and maintenance of DNA repair molecules at the sites of DSB until repair is complete, and is considered a gold standard for DSB localization.…”

Section: Introductionmentioning

confidence: 99%

Obesity alters phosphoramide mustard-induced ovarian DNA repair in mice†

Ganesan¹,

Nteeba²,

Madden³

et al. 2017

Biology of Reproduction

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Phosphoramide mustard (PM) destroys rapidly dividing cells and activates the DNA double strand break marker, γH2AX, and DNA repair in rat granulosa cells and neonatal ovaries. The effects of PM exposure on DNA damage and activation of DNA damage repair in lean and obese female mice were investigated. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice received sesame oil or PM (95%; 25 mg/kg; intraperitoneal injection). Obesity increased (P < 0.05) hepatic and spleen but decreased (P < 0.05) uterine weight. PM exposure reduced (P < 0.05) spleen weight regardless of body composition, however, decreased (P < 0.05) ovarian and hepatic weight were observed in the obese PM-exposed females. PM decreased (P < 0.05) primordial and primary follicle number in lean females. Obesity and PM increased (P < 0.05) γH2AX protein. DNA damage repair genes Prkdc, Parp1, and Rad51 mRNA were unaltered by obesity, however, Atm and Xrcc6 mRNA were increased (P < 0.05) while Brca1 was reduced (P < 0.05). Obesity reduced (P < 0.05) PRKDC, XRCC6 and but increased (P < 0.05) ATM protein. ATM, BRCA1 and RAD51 protein levels were increased (P < 0.05) by PM exposure in both lean and obese mice, while PM-induced increased (P < 0.05) XRCC6 and PARP1 were observed only in lean mice. Thus, PM induces ovarian DNA damage in vivo; obesity alters DNA repair response gene mRNA and protein level; the ovary activates DNA repair proteins in response to PM; but obesity compromises the ovarian PM response.

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“…On the basis of a radical-scavenging hypothesis, this might imply that cysteine eliminates only the radiation-induced oxygen-sensitive sites, although both sensitive and insensitive sites are basically free radicals . Kesavan, Trasi and Ahmad (1973) also observed that caffeine, a well-known radiosensitizer said to act via inhibition of biochemical repair mechanisms (Harm 1967, Bendigkeit and Hanawalt 1968, Cleaver and Thomas 1969, Domon and Rauth 1969, Yamamoto and Yamaguchi 1969, Fabre 1972, Gaudin, Gregg and Yielding 1972, Rommelaere and Errera 1972, Witte and Bohme 1972, Ahnstrom 1974, also affords partial protection against post-irradiation oxic damage (class III of Powers (1961) or A,, of Dodd and Ebert (1970)) . However, unlike cysteine, caffeine potentiates the oxygen-independent component of damage (Kesavan 1973, Kesavan and Ahmad 1974 .…”

Section: Introductionmentioning

confidence: 99%

Dependence of Chemical Radioprotection on the Stability of Radiation-induced Oxygen-sensitive Sites

Kesavan

Afzal

1975

International Journal of Radiation Biology and Related Studies

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Inhibition of DNA Repair Replication by DNA Binding Drugs Which Sensitize Cells to Alkylating Agents and X-Rays

Cited by 15 publications

References 0 publications

Differential Modification of Oxic and Anoxic Components of Radiation Damage inBacillus MegateriumSpores by Caffeine

Differential Modification of Oxic and Anoxic Components of Radiation Damage inBacillus MegateriumSpores by Caffeine

Obesity alters phosphoramide mustard-induced ovarian DNA repair in mice†

Dependence of Chemical Radioprotection on the Stability of Radiation-induced Oxygen-sensitive Sites

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