Inhibition of DNA repair by trifluoperazine

Charp, Paul A.; Regan, James D.

doi:10.1016/0167-4781(85)90026-0

Cited by 27 publications

(5 citation statements)

References 21 publications

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“…Besides a direct interaction with repair enzymes, lead and cadmium ions might also interfere with calcium-regulated processes involved in the regulation of DNA replication and repair. In this context, the specific calmodulin-inhibitor triflouperazine has been shown to inhibit the repair of UV-induced pyrimidine dimers (53) and to potentiate the lethality of bleomycin (54). Even though manifold interactions between lead and calcium concerning uptake, calcium homeostasis and substitution of lead(II) for calcium(II) have been investigated (55), their potential role in repair inhibition has yet to be elucidated.…”

Section: Cadmium(ii)mentioning

confidence: 99%

Role of DNA Repair Inhibition in Lead- and Cadmium-Induced Genotoxicity: A Review

Hartwig¹

1994

Environmental Health Perspectives

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Compounds of lead and cadmium have been shown to be carcinogenic to humans and experimental animals. However, the underlying mechanisms are still not understood. In mammalian cells in culture, lead(lIl) is weakly mutagenic after long incubation times and generates DNA strand breaks only after treatment with high, toxic doses. Cadmium(ll) induces DNA strand breaks and chromosomal aberrations, but its mutagenic potential is rather weak. However, both metals exert pronounced indirect genotoxic effects. Lead(ll) is comutagenic towards UV and N-methyl-N-nitro-Nnitrosoguanidine (MNNG) and enhances the number of UV-induced sister chromatid exchanges in V79 Chinese hamster cells. With regard to DNA repair, lead(ll) causes an accumulation of DNA strand breaks after UV-irradiation in HeLa cells, indicating an interference with the polymerization or ligation step in excision repair. Cadmium(ll) enhances the mutagenicity of UV light in V79 Chinese hamster cells and an increased sensitivity toward UV light is observed in various rodent and human cell lines. Furthermore, an inhibition of unscheduled DNA synthesis after UV-irradiation and a partial inhibition of the removal of UV-induced DNA lesions has been shown. For both metals, the indirect genotoxic effects are observed at low, nontoxic concentrations, suggesting that an interference with DNA repair processes may be predominant at biologically relevant concentrations. This might also explain the conflicting results of epidemiological studies obtained for both metals. Possible mechanisms of repair inhibiton are discussed.-Environ Health Perspect 102(Suppl 3): 45-50 (1994).

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Section: Cadmium(ii)mentioning

confidence: 99%

Role of DNA Repair Inhibition in Lead- and Cadmium-Induced Genotoxicity: A Review

Hartwig¹

1994

Environmental Health Perspectives

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“…Calmodulin is thought to influence DNA repair. Calmodulin inhibitors, such as TFP, may inhibit one or more steps in DNA repair (27,28). TFP inhibited DNA-PK activity in both U-1810 cell extracts and in commercially purified enzyme (Figs.…”

Section: Figmentioning

confidence: 97%

DNA-Dependent Protein Kinase Is Inhibited by Trifluoperazine

Eriksson

Yachnin

Lewensohn

et al. 2001

Biochemical and Biophysical Research Communications

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“…Phenothiazines have been shown to be able to inhibit the DNA-dependent protein kinase in vitro (52), as a result of which the effectivity of DNA repair is lower; however, they are also purported to interfere with further DNA-repair processes (53). This assumption is based on the observation that phenothiazines reduce endonuclease activity in human fibroblast cells, which plays an important role in the DNA-repair mechanisms (54). However, phenothiazines can exert an effect on checkpoint proteins not only directly but indirectly as well.…”

Section: Antitumor Effectmentioning

confidence: 99%

Possible Biological and Clinical Applications of Phenothiazines

Varga

Csonka

et al. 2017

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Abstract. Phenothiazines have been used in many areasPhenothiazines are unanimously one of the most versatile compounds from the view of biological activity. Since their discovery, new exploitable pharmacological properties have emerged from time to time; thus, they have an important role in many areas of medicine and beyond. This is why phenothiazines are basic compounds in pharmacology. The history of these compounds goes back to the second half of the 19th century, when a German chemist, Heinrich August Bernthsen began to study the structure of methylene blue, which was first synthesized in 1876 by Heinrich Caro. In 1885, two years after Bernthsen first managed to produce phenothiazine, he also succeeded in describing the structure of methylene blue (1). At the same time, Paul Ehrlich began to investigate the possible therapeutic use of methylene blue in malaria infections, which he first published in 1891 (2). Due to this, methylene blue was often prescribed for patients with malaria in the subsequent period (3).Research conducted in the 1930s and '40s proved the potential wide use of phenothiazines. The insecticidal (4), antihelmintic (5, 6), and antibacterial (7) effects of the compound were detected; however, it was not widely used for these purposes. In the 1940s, another novel phenothiazine derivative, namely promethazine was brought to the forefront of attention; it was investigated by Paul Charpentier at the Rhone-Poulenc laboratory in Paris (8). It was shown that promethazine had an antihistamine effect (9), which was later used in the therapy of allergic diseases and in anesthesia (10,11). A few years later in the same laboratory, chlorpromazine was discovered, which has strong anxiolytic and antipsychotic effect along with its antihistaminic effect (12). Psychiatry fully exploited this feature in psychotic patients (13), which resulted in the almost complete emptying of psychiatric hospitals in the 1950s. As a result, the discovery of chlorpromazine and the beginning of its use as an antipsychotic are considered the beginning of modern psychiatry and psychopharmacology.Since then, several antipsychotic phenothiazine compounds have been used in clinical practice, although research conducted in the last couple of decades indicated that phenothiazine compounds could have an important role in other fields of medicine as well, such as in the treatment of tumorous, infectious, or neurodegenerative diseases (3). 5983

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Inhibition of DNA repair by trifluoperazine

Cited by 27 publications

References 21 publications

Role of DNA Repair Inhibition in Lead- and Cadmium-Induced Genotoxicity: A Review

Role of DNA Repair Inhibition in Lead- and Cadmium-Induced Genotoxicity: A Review

DNA-Dependent Protein Kinase Is Inhibited by Trifluoperazine

Possible Biological and Clinical Applications of Phenothiazines

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