TY  - JOUR
AU  - Schröder, H.C.
AU  - Wenger, R.
AU  - Gerner, H.
AU  - Reuter, P.
AU  - Kuchino, Y.
AU  - Sladić, Dušan
AU  - Mülle, W.E.G.
PY  - 1989
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/15
AB  - The amino acid L-tryptophan is known to be a modulator of many processes of cell metabolism. In this contribution we show that L-tryptophan interferes with some biological effects of the antileukemic and anti-human immunodeficiency virus agent avarol, possibly by different mechanisms. Avarol has been shown to be able to modulate posttranscriptional events of mRNA synthesis, resulting in an increase of the base-sequence complexities of the nonabundant and rare mRNA classes. Here it is demonstrated that this change in mRNA abundancy distribution is accompanied by an increase in the level of some specific, low abundant mRNAs (ras and c-myc). Addition of L-tryptophan was found to abolish avarol-caused gene relaxation in 1,1210 mouse leukemia cells. In addition, L-tryptophan suppressed the induction of γ-interferon mRNA production in human peripheral blood lymphocytes. At the level of DNA, L-tryptophan inhibited the production of strand breaks by cytotoxic avarol concentrations in Friend erythroleukemia cells in vitro. Moreover, it competed with avarol for binding to the nuclear envelope binding site; this effect was not shown by other amino acids. © 1989, American Association for Cancer Research. All rights reserved.
T2  - Cancer Research
T1  - Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan
VL  - 49
IS  - 8
SP  - 2069
EP  - 2076
UR  - https://hdl.handle.net/21.15107/rcub_cherry_15
ER  - 

@article{
author = "Schröder, H.C. and Wenger, R. and Gerner, H. and Reuter, P. and Kuchino, Y. and Sladić, Dušan and Mülle, W.E.G.",
year = "1989",
abstract = "The amino acid L-tryptophan is known to be a modulator of many processes of cell metabolism. In this contribution we show that L-tryptophan interferes with some biological effects of the antileukemic and anti-human immunodeficiency virus agent avarol, possibly by different mechanisms. Avarol has been shown to be able to modulate posttranscriptional events of mRNA synthesis, resulting in an increase of the base-sequence complexities of the nonabundant and rare mRNA classes. Here it is demonstrated that this change in mRNA abundancy distribution is accompanied by an increase in the level of some specific, low abundant mRNAs (ras and c-myc). Addition of L-tryptophan was found to abolish avarol-caused gene relaxation in 1,1210 mouse leukemia cells. In addition, L-tryptophan suppressed the induction of γ-interferon mRNA production in human peripheral blood lymphocytes. At the level of DNA, L-tryptophan inhibited the production of strand breaks by cytotoxic avarol concentrations in Friend erythroleukemia cells in vitro. Moreover, it competed with avarol for binding to the nuclear envelope binding site; this effect was not shown by other amino acids. © 1989, American Association for Cancer Research. All rights reserved.",
journal = "Cancer Research",
title = "Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan",
volume = "49",
number = "8",
pages = "2069-2076",
url = "https://hdl.handle.net/21.15107/rcub_cherry_15"
}

Schröder, H.C., Wenger, R., Gerner, H., Reuter, P., Kuchino, Y., Sladić, D.,& Mülle, W.E.G.. (1989). Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan. in Cancer Research, 49(8), 2069-2076.
https://hdl.handle.net/21.15107/rcub_cherry_15

Schröder H, Wenger R, Gerner H, Reuter P, Kuchino Y, Sladić D, Mülle W. Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan. in Cancer Research. 1989;49(8):2069-2076.
https://hdl.handle.net/21.15107/rcub_cherry_15 .

Schröder, H.C., Wenger, R., Gerner, H., Reuter, P., Kuchino, Y., Sladić, Dušan, Mülle, W.E.G., "Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan" in Cancer Research, 49, no. 8 (1989):2069-2076,
https://hdl.handle.net/21.15107/rcub_cherry_15 .

TY  - JOUR
AU  - Muller, W.E.G.
AU  - Sladić, Dušan
AU  - Zahn, R.K.
AU  - Bassler, K.-H.
AU  - Dogovic, N.
AU  - Gerner, H.
AU  - Gasic, M.J.
AU  - Schroder, H.C.
PY  - 1987
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/13
AB  - The hydroquinone-containing cytostatic compound avarol inhibits predominantly growth of those cell lines which have a low level of superoxide dismutase. The substrate of this enzyme, the superoxide anion, was found to be formed during the in vitro oxidation reaction of avarol to its semiquinone radical in the presence of oxygen. Under the same incubation conditions plasmid DNA (pBR322) was converted from the fully supercoiled circular form mainly to the nicked circular form, indicating that the compound causes primarily single-strand breaks. Using Friend erythroleukemia cells (FLC) it was found that avarol induces a dose-dependent DNA damage; the maximum number of DNA strand breaks was observed at 5 h after addition of the compound to the cells. Removal of avarol resulted in a rapid DNA rejoining with biphasic repair kinetics [first half-time, 8 min (90% of the breaks) and a second half-time, 40 min (10% of the breaks)]. When the degree of avarol-induced DNA damage in FLC was compared with the drug-caused inhibition of cell growth a close correlation was established. Avarol displayed no effect on dimethyl sulfoxide-induced erythrodifferentiation of FLC as determined by the benzidine reaction and by dot blot hybridization experiments. From incubation studies of FLC with [3H]avarol no hint was obtained for the formation of an adduct between DNA and the compound. The subcellular distribution of [3H]avarol was studied in liver cells after i.v. application of the compound. The predominant amount of the compound was present in the cytosolic fraction; little avarol was associated with plasma membranes, nuclei, and mitochondria. Using (a) oxidative phosphorylation and (b) oxygen uptake as parameters for mitochondrial function, no effect of the compound on the activity of this organelle was determined. These results suggest that avarol forms superoxide anions (and in consequence possibly also hydroxyl radicals) especially in those cells which have low levels of superoxide dismutase. Moreover, evidence is provided that the active oxygen species cause DNA damage resulting in the observed cytotoxic effect.
T2  - Cancer Research
T1  - Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells
VL  - 47
IS  - 24 I
SP  - 6565
EP  - 6571
UR  - https://hdl.handle.net/21.15107/rcub_cherry_13
ER  - 

@article{
author = "Muller, W.E.G. and Sladić, Dušan and Zahn, R.K. and Bassler, K.-H. and Dogovic, N. and Gerner, H. and Gasic, M.J. and Schroder, H.C.",
year = "1987",
abstract = "The hydroquinone-containing cytostatic compound avarol inhibits predominantly growth of those cell lines which have a low level of superoxide dismutase. The substrate of this enzyme, the superoxide anion, was found to be formed during the in vitro oxidation reaction of avarol to its semiquinone radical in the presence of oxygen. Under the same incubation conditions plasmid DNA (pBR322) was converted from the fully supercoiled circular form mainly to the nicked circular form, indicating that the compound causes primarily single-strand breaks. Using Friend erythroleukemia cells (FLC) it was found that avarol induces a dose-dependent DNA damage; the maximum number of DNA strand breaks was observed at 5 h after addition of the compound to the cells. Removal of avarol resulted in a rapid DNA rejoining with biphasic repair kinetics [first half-time, 8 min (90% of the breaks) and a second half-time, 40 min (10% of the breaks)]. When the degree of avarol-induced DNA damage in FLC was compared with the drug-caused inhibition of cell growth a close correlation was established. Avarol displayed no effect on dimethyl sulfoxide-induced erythrodifferentiation of FLC as determined by the benzidine reaction and by dot blot hybridization experiments. From incubation studies of FLC with [3H]avarol no hint was obtained for the formation of an adduct between DNA and the compound. The subcellular distribution of [3H]avarol was studied in liver cells after i.v. application of the compound. The predominant amount of the compound was present in the cytosolic fraction; little avarol was associated with plasma membranes, nuclei, and mitochondria. Using (a) oxidative phosphorylation and (b) oxygen uptake as parameters for mitochondrial function, no effect of the compound on the activity of this organelle was determined. These results suggest that avarol forms superoxide anions (and in consequence possibly also hydroxyl radicals) especially in those cells which have low levels of superoxide dismutase. Moreover, evidence is provided that the active oxygen species cause DNA damage resulting in the observed cytotoxic effect.",
journal = "Cancer Research",
title = "Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells",
volume = "47",
number = "24 I",
pages = "6565-6571",
url = "https://hdl.handle.net/21.15107/rcub_cherry_13"
}

Muller, W.E.G., Sladić, D., Zahn, R.K., Bassler, K.-H., Dogovic, N., Gerner, H., Gasic, M.J.,& Schroder, H.C.. (1987). Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells. in Cancer Research, 47(24 I), 6565-6571.
https://hdl.handle.net/21.15107/rcub_cherry_13

Muller W, Sladić D, Zahn R, Bassler K, Dogovic N, Gerner H, Gasic M, Schroder H. Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells. in Cancer Research. 1987;47(24 I):6565-6571.
https://hdl.handle.net/21.15107/rcub_cherry_13 .

Muller, W.E.G., Sladić, Dušan, Zahn, R.K., Bassler, K.-H., Dogovic, N., Gerner, H., Gasic, M.J., Schroder, H.C., "Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells" in Cancer Research, 47, no. 24 I (1987):6565-6571,
https://hdl.handle.net/21.15107/rcub_cherry_13 .