Induction of micronuclei by bleomycin in G<sub>0</sub> human lymphocytes: II. Potentiation by radioprotectors

Gr, Hoffmann; Sp, Colyer; Lg, Littlefield

doi:10.1002/em.2850210207

Cited by 17 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Radioprotectors, such as DMSO, 2-[(aminopropyl)amino] ethanethiol (WR-1065) (Hoffman et al, 1993) and cysteamine (Hoffman and Littlefield, 1995), potentiated the clastogenic activity of BLM in G o human lymphocytes. In contrast, WR-1065 has been reported to protect against the effects of BLM in cultured Chinese hamster cells (Nagy and Grdina, 1986).…”

Section: Discussionmentioning

confidence: 99%

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Araújo

Dias²,

Kronka

et al. 1999

Genet. Mol. Biol.

View full text Add to dashboard Cite

Cell culture and treatmentsChinese hamster ovary cells (CHO-9 cell line) were kindly supplied by Prof. A.T. Natarajan (University of Leiden, The Netherlands). Cells were maintained as monolayers growing at 37°C in 25-cm 2 flasks (Corning) containing HAM-F10 (Sigma) plus DMEM (Dulbecco's modi- ABSTRACT Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberration frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 and 500 µg/ ml) and curcumin (2.5, 5 and 10 µg/ml), were combined with BLM (10 µg/ml) in CHO cells treated during the G 1 /S, S or G 2 /S phases of the cell cycle. Neither turmeric nor curcumin prevented BLM-induced chromosomal damage in any phases of the cell cycle. Conversely, a potentiation of the clastogenicity of BLM by curcumin was clearly observed in cells treated during the S and G 2 /S phases. Curcumin was also clastogenic by itself at 10 µg/ml in two protocols used. However, the exact mechanism by which curcumin produced clastogenic and potentiating effects remains unknown.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Araújo

Dias²,

Kronka

et al. 1999

Genet. Mol. Biol.

View full text Add to dashboard Cite

show abstract

“…The potentiation of BLM by aminothiols is apparently limited to assays with sufficient oxygen, such as those in fresh G 0 lymphocytes. WR-1065 [Hoffmann et al, 1993b[Hoffmann et al, , 1994 strongly potentiates BLM in G 0 lymphocytes. The concentration of BLM required to cause a given level of chromosomal damage in the presence of WR-1065 is as much as 500-fold lower than that in its absence [Hoffmann et al, 1994].…”

Section: Discussionmentioning

confidence: 92%

“…Potentiation of the genetic activity of BLM has been observed with CSM , cysteine [Chatterjee and JacobRaman, 1993], glutathione [Chatterjee et al, 1989;Chattopadhyay et al, 1997], and WR-1065 [Hoffmann et al, 1993b[Hoffmann et al, , 1994. Protective effects have also been ascribed to CSM , cysteine [Chatterjee and Jacob-Raman, 1993], and WR-1065 [Nagy and Grdina, 1986;Hoffmann et al, , 1999.…”

Section: Discussionmentioning

confidence: 99%

“…WR-1065 potentiates the clastogenicity of BLM in G 0 human lymphocytes [Hoffmann et al, 1993b[Hoffmann et al, , 1994 but reduces its mutagenicity in Chinese hamster V79 cells [Nagy and Grdina, 1986]. Studies in yeast under hypoxic and oxygenated conditions help reconcile this inconsistency by showing that the availability of oxygen is a critical factor in the nature of the interaction between BLM and aminothiols .…”

Section: Discussionmentioning

confidence: 99%

“…The difference among systems apparently depends on physiological conditions, most notably oxygen tensions . WR-1065 [Hoffmann et al, 1993b[Hoffmann et al, , 1994 and the related aminothiol radioprotector CSM -BLM [Hoffmann et al, 1994]. As a diamine, WR-1065 binds to DNA [Smoluk et al, 1988a;Sy et al, 1999] and may alter DNA conformation so as to facilitate BLM action.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Structure–activity analysis of the potentiation by aminothiols of the chromosome‐damaging effect of bleomycin in G₀ human lymphocytes

Hoffmann

Buccola

Merz

et al. 2001

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

The radioprotective aminothiols 2-[(aminopropyl)amino] ethanethiol (WR-1065) and cysteamine (CSM) potentiate the induction of chromosomal damage by the radiomimetic compound bleomycin (BLM) in G0 human lymphocytes. To investigate the mechanism of potentiation, we measured the clastogenic activity of BLM in the cytokinesis-block micronucleus assay in the presence and absence of amines, thiols, and aminothiols. The hydroxy analog of WR-1065, 2-(3-aminopropylamino) ethanol (WR-OH), potentiates BLM only slightly, indicating the critical nature of the thiol group. As thiols, WR-1065 and CSM may donate electrons for the activation of Fe(+2)-BLM or for the regeneration of Fe(+2)-BLM from inactive Fe(+3)-BLM. The amines putrescine, spermidine, and spermine all potentiate BLM, but they are weaker potentiators than the aminothiols, and they are effective only at high concentrations. Their activity, like that of WR-OH, is probably a consequence of conformational alteration of DNA. Dithioerythritol (DTE) and 2-mercaptoethanol (2-ME), thiols lacking an amino group, are less effective potentiators of BLM than are the aminothiols. The thiol group of WR-1065 and CSM is therefore essential, but insufficient, for explaining the strong enhancement of BLM activity. The cationic nature of CSM and WR-1065, conferred by the amino groups, evidently concentrates the active thiol function at the site of BLM action on DNA. As expected on this basis, the diamine WR-1065 is a more effective potentiator of BLM than is the monoamine CSM, whereas cysteine and N-acetylcysteine (NAC), which lack a net positive charge, potentiate BLM only weakly. These studies suggest that potentiation of the clastogenic action of BLM by aminothiols can be explained by the combination of a thiol-mediated redox mechanism and an amine-mediated targeting of the thiol function to DNA.

show abstract

Analysis by FISH of the spectrum of chromosome aberrations induced by X-rays in G0 human lymphocytes and their fate through mitotic divisions in culture

Hoffmann¹,

Sayer²,

Joiner³

et al. 1999

Environ. Mol. Mutagen.

Self Cite

View full text Add to dashboard Cite

The induction, distribution, and persistence of chromosome aberrations in human lymphocytes exposed to X‐rays in G0 were analyzed in 48‐, 70‐, and 94‐hr cultures by conventional metaphase analysis and painting of chromosomes 1, 2, and 4 by FISH. All cells that had been scored by FISH were relocated to determine by differential staining of chromatids whether they had passed through 1, 2, or ≥3 divisions. FISH revealed a dose‐dependent induction of stable and unstable aberrations, while chromatid labeling showed mitotic lag caused by irradiation in G0. Relative to their DNA contents, there was a small but significant overrepresentation of chromosome 4 and underrepresentation of chromosome 2 among the aberrations involving chromosomes 1, 2, and 4. FISH slightly underestimated the genomic frequency of unstable aberrations measured by conventional metaphase analysis. There was a slight excess of translocations relative to dicentrics, but the data are compatible with the 1:1 ratio expected from cytogenetic theory. Many of the translocations were apparently incomplete (i.e., nonreciprocal). Incomplete translocations were more frequent at higher X‐ray dose and in first division, suggesting that they may be associated with complex damage and are more apt to be lost in mitosis than complete translocations. Among the incomplete translocations, t(Ab) outnumbered t(Ba) — a difference ascribable to the FISH technique. Aberration frequencies declined as the cells divided in culture. The overall decline in the frequency of aberrant cells (≈29% per cell generation) reflects a rapid decline in dicentrics and fragments (≈60% per cell generation) and the relative stability of translocations. The frequency of translocation‐bearing cells underwent a modest decline in culture (≈13% per cell generation). Environ. Mol. Mutagen. 33:94–110, 1999 © 1999 Wiley‐Liss, Inc.

show abstract

Induction of micronuclei by bleomycin in G₀ human lymphocytes: II. Potentiation by radioprotectors

Cited by 17 publications

References 30 publications

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Structure–activity analysis of the potentiation by aminothiols of the chromosome‐damaging effect of bleomycin in G₀ human lymphocytes

Analysis by FISH of the spectrum of chromosome aberrations induced by X-rays in G0 human lymphocytes and their fate through mitotic divisions in culture

Contact Info

Product

Resources

About

Induction of micronuclei by bleomycin in G0 human lymphocytes: II. Potentiation by radioprotectors

Cited by 17 publications

References 30 publications

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Structure–activity analysis of the potentiation by aminothiols of the chromosome‐damaging effect of bleomycin in G0 human lymphocytes

Analysis by FISH of the spectrum of chromosome aberrations induced by X-rays in G0 human lymphocytes and their fate through mitotic divisions in culture

Contact Info

Product

Resources

About

Induction of micronuclei by bleomycin in G₀ human lymphocytes: II. Potentiation by radioprotectors

Structure–activity analysis of the potentiation by aminothiols of the chromosome‐damaging effect of bleomycin in G₀ human lymphocytes