Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice.
TL;DR: The hypothesis that prolonged Fen application induces dose-dependent increase in post-replication repair and caffeine enhanced toxicity by inhibiting repair process(es) is supported and the study suggests that Fen is a clastogen and since caffeine may have a synergistic effect, it should be avoided during treatment.
Abstract: Fenfluramine (Fen), an amphetamine-derivative widely used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice for assessing its clastogenic potentials. Concentrations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were administered orally for the study. Long-term treatment for 21 days showed dose-dependent significant increase in chromosomal aberrations on the 8th day. A significant decrease in aberration levels was seen in the late treatment period. Caffeine alone produced dose-and duration-dependent clastogcnicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given by gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares. The results support the hypouhesis that prolonged Fen application induces dose-dependent increase in post-replication repair and...
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TL;DR: Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity, which may be an additional burden in people using anorectic drugs.
Abstract: Context: Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approv...
13 citations
Cites background from "Potentiation by caffeine of the fre..."
...Its antigenotoxic (Geriyol et al., 2015; Sen et al., 1994), antioxidant (Zheng et al., 2004) and anticancer activities (Sabisz & Skladanowski, 2008) are well established....
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...On the contrary, Sen et al. (1994) reported that caffeine acted synergistically with another antiobesity drug-fenfluramine and increased chromosome aberrations over a period of time....
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...Its antigenotoxic (Geriyol et al., 2015; Sen et al., 1994), antioxidant (Zheng et al....
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TL;DR: The Structures of the uvr Genes and Proteins, and the Action Mechanism of ABC Excinuclease, are described.
Abstract: DIRECT REPAIR: DNA PHOTOLYASES.. . . . ......... . ......... 31 Escherichia Coli Photolyase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 31 Saccharomyces Cerevisiae Photolyase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Streptomyces Griseus Photolyase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 BASE-EXCISION REPAIR 38 DNA Glycosylases . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . 39 DNA Glycosylase-AP E ndonucleases . . . . . . ... . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . ..... . . . . . . . . . 42 AP Endol ucleases 43 Deoxyribose Phosphatase 46 NUCLEOTIDE-EXCISION REPAIR......... . . .. . . 46 Genetics of N ucleotide-Excision Repair .. . .... . . . . . .. . . . . . . . . . . . ....... . .. . . . . . . .. ......... . . 47 The Substrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 The Structures of the uvr Genes and Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 49 The Action Mechanism of ABC Excinuclease . . ... . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . . . .. . . . . . . . 51 The Turnover of ABC Excinuclease 54 Nucleotide Excision Repair in Other Bacteria . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 57 Nucleotide Excision Repair in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 RECOMBINATIONAL REPAIR .. ........ . . . . . ......... . . . . .... . . . .. . . . . . ... . . . . . 58 REPAIR OF CROSSLINKS . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . .. . .. . . . . 60 REGULATION OF DNA REPAIR..... . . . ......... . . . . . . . ...... . . .. .. ........ . . ... ..... 61 The SOS Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . ..... 61 Adaptation.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 62 Adaptive Response to Oxidative Stress 62
774 citations
TL;DR: Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.
Abstract: Cells cultured from most patients suffering from the sunlight-sensitive hereditary disorder xeroderma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA. There is, however, one class of these patients whose cells are completely normal in this excision repair process. We have found that these cells have an abnormality in the manner in which DNA is synthesized after UV-irradiation. The time taken to convert initially low-molecular-weight DNA synthesized in UV-irradiated cells into high-molecular-weight DNA similar in size to that in untreated cells is much greater in these variants than in normal cells. Furthermore, this slow conversion of low to high-molecular-weight newly synthesized DNA is drastically inhibited by caffeine, which has no effect in normal cells. Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.
616 citations
Book•
01 Oct 1959
TL;DR: In this article, the authors report critical values (to four significant figures) which have been found by inverse interpolation in the new table of the probability integral of the studentized range.
Abstract: Abstract : The purpose of this paper is to report critical values (to four significant figures) which have been found by inverse interpolation in the new table of the probability integral of the studentized range. Included are corrected tables for significance levels alpha = 0.05, 0.1 and new tables for significance levels alpha = 0.10, 0.005, 0.001-all with sample sizes n = 2(1) 20(2)40(10)100 and degrees of freedom nu = 1(1)20, 24, 30, 60, 120, infinity.
614 citations
TL;DR: In this paper, the authors report critical values (to four significant figures) which have been found by inverse interpolation in the new table of the probability integral of the studentized range.
Abstract: : The purpose of this paper is to report critical values (to four significant figures) which have been found by inverse interpolation in the new table of the probability integral of the studentized range. Included are corrected tables for significance levels alpha = 0.05, 0.1 and new tables for significance levels alpha = 0.10, 0.005, 0.001-all with sample sizes n = 2(1) 20(2)40(10)100 and degrees of freedom nu = 1(1)20, 24, 30, 60, 120, infinity.
579 citations
479 citations