Effect of a Hypoxic Radiosensitizer, AK 2123 (Sanazole), on Yeast Saccharomyces cerevisiae

Abstract

Sanazole/DNA repair/Hypoxic radiosensitization/DNA polymerases/Saccharomyces cerevisiae Yeast Saccharomyces cerevisiae can exist in two physiological states, namely anaerobic and aerobic. They differ in their response to gamma- radiation and radiomodification. We report hereon our results concerning radiosensitization by Sanazole (AK-2123), a well-known hypoxic radio sensitizer, whose mechanism of action has been studied extensively. The results have revealed that Sanazole (1 mM) when present during irradiation could specifically sensitize wild-type anaerobic yeast cells with a DMF of 2.4. In a radiation-sensitive mutant which lacks a DNA repair pathway specific for the recovery from gamma-radiation induced DNA damage, the extent of sensitization was considerably lower and the DMF was only 1.3. Studies on the liquid holding recovery of cells of both wild- type and rad52 yeast cells exposed to radiation in presence of Sanazole revealed that sensitization by Sanazole is due to a preferential increase in the DNA damage, and not by impairing DNA repair. This system thus holds promise for screening potential hypoxic chemical radiosensitizers.

Enhancement of radiation-induced apoptosis of human lymphoma U937 cells by sanazole

“…Because the experiments were conducted when the tumor in mice was grown to a diameter of 6-8 mm, the cellular center of tumor may be in hypoxic. Another study showed that sanazole (1 mM) when presented during irradiation could specifically sensitize wild-type anaerobic yeast cells [11]. In this present study, our data showed the combination of sanazole (10 mM) and IR significantly increased apoptosis of human lymphoma cells induced by IR in aerobic condition.…”

“…The nitroimidazole group of radiosensitizing agents (including sanazole) is considered to sensitive hypoxic cells selectively by capturing macromolecular free radicals, thereby acting to fix damage as well as to inhibit DNA repair [10]. Studies on the wild-type and mutant rad 52 yeast cells exposed to radiation in the presence of sanazole revealed that sensitization by sanazole is due to a preferential increase in DNA damage (DNA strand break due to free radicals), and not by impairing DNA repair [11]. It is known that DNA damage can enhance apoptosis, as demonstrated in studies with the nitroimidazole analogue doranidazole [12].…”

Indigowood root extract protects hematopoietic cells, reduces tissue damage and modulates inflammatory cytokines after total-body irradiation: Does Indirubin play a role in radioprotection?

“…Damages caused to DNA by ionizing radiation can result in the loss of viability of the cells exposed to radiation. The factors that influence the response of living cells to radiation are tissue type, DNA repair status of damaged cells, local circulation, and physiological status (Pasupathy et al 2001). In Chinese medicine, radiation could cause so called ''toxic heat'', which can increase inflammatory fever, cause blood damage, loss of intercellular liquid and energy.…”

Induction of maize chromosome altered plants by seeds irradiation pre-soaked in metronidazole

“…In addition, the literature has emphasized mainly the radiation dosage (SANTOS 1993;LATHA and NAIR 1999;IOSHIHIDE and ATSUO 1998), as well the presence of some chemical substances (VICCINI et al 1997b;PACINI et al 1999, PASUPATHY et al 2001.…”

“…Among the more known radiosensitizing substances, some drugs such as metronidazole, misonidazole (RO-0582), (HALL 1982), sanazole (AK-2123), (PASUPATHY et al 2001), sodium azide (AS) (MONTALVAN and ANDO 1998), diethyl sulfate (DES), ethyl-metane sulfonate (EMS) (KUMAR and DUBEY 1998) and some timine analogous such as 5-Brdu, 5-Cldu (GREER et al 2001) are the most important ones.…”