Linear Correlation between Surviving Fraction and the Micronucleus Frequency

E, Wandl; Ono, Koji; Kain, Renate; Herbsthofer, T; Hienert, G; Höbarth, K.

doi:10.1080/09553008914552031

Cited by 56 publications

(18 citation statements)

References 6 publications

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“…Several authors have reported a good quantitative inverse relationship between micronucleus frequency and clonogenic survival (Wandl et al, 1989;Jamali and Trott, 1996;Mariya et al, 1997); however, there are also several reports in which such a correlation was not found (Bush and McMillan, 1993;Slavotinek et al, 1993;Villa et al, 1994). Some authors have reported an inverse correlation between apoptotic frequency and cell survival (Radford and Murphy, 1994;Olive and Durand, 1997;Guo et al, 1999), whereas others found no correlation (Yangihara et al, 1995;McKenna et al, 1996).…”

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confidence: 88%

Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

Dunne¹,

Price²,

Mothersill³

et al. 2003

Br J Cancer

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The intrinsic radiation sensitivity of normal and tumour tissue is a major determinant of the outcome of radiotherapy. There is currently no established test that can be used routinely to measure the radiosensitivity of the cells in an individual patient's cancer in a manner that can inform treatment planning. The purpose of this study was to evaluate, in four human colorectal adenocarcinoma cell lines, two possible end points as surrogate markers of radiation response -apoptosis and induction of DNA single-strand breaksand to compare the results with those of a conventional clonogenic assay. Cell lines (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured using the clonogenic assay. Apoptosis was determined on the basis of morphology under fluorescent microscopy and DNA damage/repair was measured, as tail moment, using an adaptation of the alkaline comet assay. The relationship between surviving fraction at 2 Gy (SF 2 ) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF 2 . Initial damage measured after 2 Gy using the alkaline comet assay gave a close correlation with SF 2 (r 2 ¼ 0.95), whereas there was no correlation between initial DNA damage repair rate and SF 2 .

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mentioning

confidence: 88%

Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

Dunne¹,

Price²,

Mothersill³

et al. 2003

Br J Cancer

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“…The production of micronuclei is considered to be linked to cell death (Joshi et al, 1982;Campbell & Warenius, 1989) and a correlation has been reported between the MN fre- (Wandl et al, 1989;. In such cases, the best parameter of radiation response is unknown.…”

Section: Assai Proceduresmentioning

confidence: 99%

Assessment of the proliferative activity and radiosensitivity of human tumours using the cytokinesis-block micronucleus assay

Shibamoto

Shibata²,

Miyatake³

et al. 1994

Br J Cancer

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Sm_uary We established an in vitro cytokinesis-block micronucleus assay of human tumours for estimation of the proportion of cells undergoing mitosis (the dividing fraction, DF), the time for the number of nuclei to double and the radiosensitivity in terms of the micronucleus frequency, based on a concept described previously. Under certain conditions, the nuclear number doubling time (NNDT) Recently, the importance of an individualised approach to cancer therapy based on the biological characteristics of each patient's tumour has been increasingly stressed. In radiation therapy, the prediction of biological parameters such as the intrnsic radiosensitivity, proliferative activity (especially the potential doubling time: Tpo) and degree of hypoxia would be helpful in planning optimal treatment (Peters et al., 1988). Several assay systems have been developed to estimate these parameters (Begg et al., 1988;Peters et al., 1988;Brock et al., 1989; H6ckel et al., 1993), but newer and better assays are needed because all of the existing ones have some disadvantages. In addition, none of the assays allows two or more parameters to be estimated simultaneously.In our previous studies using xenografted human and mouse tumours , we developed a new method of estimating tumour radiosensitivity and proliferative activity, which involved determining the micronucleus (MN) frequency after irradiation, the fraction of tumour cells undergoing mitosis in vitro (the dividing fraction, DF) and the presumed time for the number of tumour cell nuclei to double in vitro (nuclear number doubling time, NNDT). The NNDT is considered to be similar to Tpot provided that the culture conditions do not alter karyokinesis. This method makes use of the cytokinesisblock MN assay (Fenech & Morley, 1985) Materals and methodsTumour specimens All specimens were obtained at the time of major surgery and not by biopsy. A total of 73 solid tumours resected from patients without preoperative irradiation or chemotherapy were evaluated. Malignant ascites from a patient with pancreatic cancer was also investigated, but we could not obtain a result because of excessive contamination with nonmalignant cells. Since the first aim of this study was to determine the types of tumours suitable for this assay, a variety of lesions were studied irrespective of their suitability for post-operative radiotherapy. The tumours ranged from 50 mg to 4.0 g in weight, with a median weight of 850 mg. Assai procedureThe method used was similar to that of previous studies with slight modifications. The current standard procedure was performed as follows. Tumour specimens were minced with scissors and treated at 3TC for 2 h with 1 mg ml-' collagenase/dispase (Boehringer, Mannheim, Germany) dissolved in phosphate-buffered saline. Then the resulting tumour cell suspension was filtered through a fine wire mesh and viable cells were counted using trypan blue. The proportion of viable cells ranged from 25% to more than 90%, and the cell yield ranged between 1 x 106 and 7 x 10' per gr...

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“…Reports about correlation between micronucleus frequency and reproductive cell death are controversial. A good correlation between clonogenic cell survival and micronucleus frequency in tumour cell lines was presented by several investigators (Wandl et al, 1989;Stap and Aten, 1990;Bakker et al, 1993). However, other studies brought contrasting results (Bush and McMillan, 1993;Slavotinek et al, 1993;Villa et al, 1994;Champion et al, 1995), indicating that lethal events measured as surviving fraction not always coincide with MN frequency.…”

Section: Discussionmentioning

confidence: 90%

“…Since micronuclei arise from disturbed genetic materials such as acentric chromosomal fragments (Heddle and Carrano, 1977), or even whole chromosomes (Weissenborn and Streffer, 1991), the cells containing micronuclei are potentially dead. Some experiments on established normal cell lines (Midander and Revesz, 1980), on human tumour xenografts (Shibamoto et al, 1991) and on early passages of human tumour cells (Wandl et al, 1989) indicated good correlation between radiation-induced micronucleus frequency and clonogenic cell survival. Our own study on…”

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confidence: 99%

The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability

et al. 1999

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Summary A potential usefulness of micronucleus assay for prediction of tumour radiosensitivity has been tested in 64 patients with advanced stage (II B-IV B) cervical carcinoma treated by radiotherapy. The study of cellular radiosensitivity in vitro was conducted in parallel with the study of cellular damage after tumour irradiation in vivo. Radiosensitivity of in vitro cultured primary cells isolated from tumour biopsies taken before radiotherapy was evaluated using cytokinesis-block micronucleus assay. Frequency of micronuclei per binucleated cell (MN/BNC) at 2 Gy was used as a measure of radiosensitivity. Radiation sensitivity in vivo was expressed as per cent increment of micronucleus frequency in cells isolated from biopsy taken after 20 Gy (external irradiation, 10 × 2 Gy) over the pre-treatment spontaneous micronucleus level and was called MN20. Very low correlation (r = 0.324) was observed between micronucleus frequency in vitro and in vivo. Although micronucleus frequency at 2 Gy differed widely between tumours evaluated (mean MN/BNC was 0.224; range 0.08-0.416), no significant correlation was observed between this parameter and clinical outcome. The average increment of micronucleus frequency after 20 Gy amounted to 193% of spontaneous level (range 60-610%) and was independent of spontaneous micronucleation before radiotherapy. In contrast to in vitro results, these from in vivo assay seem to have a predictive value for radiotherapy of cervix cancer. The micronucleus increment in vivo that reached at least 117.5% of pretreatment value (first quartile for MN20 data set) correlated significantly with better tumour local control (P < 0.008) and overall survival (P < 0.045). Our results suggest that evaluation of increment of micronucleus frequency during radiotherapy (after fixed tested dose of 20 Gy) offers a potentially valuable approach to predicting individual radioresponsiveness and may be helpful for individualization of treatment strategy in advanced stage cervical cancer.

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Linear Correlation between Surviving Fraction and the Micronucleus Frequency

Cited by 56 publications

References 6 publications

Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

Assessment of the proliferative activity and radiosensitivity of human tumours using the cytokinesis-block micronucleus assay

The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability

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