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W Dörr

Publications and source records attributed to W Dörr.

67 records · Page 4Linked to original sources
PubMed1993

Capacity and kinetics of SLD repair in mouse tongue epithelium.

The effect of dose fractionation on the radiation response of mouse tongue epithelium was quantified in fractionation protocols involving 1, 3, 4, 5 and 10 fractions, separated by at least 4 h. Fractionated irradiation was given either to the whole snout by 300 kV X-rays or locally to the tongue using 25 kV X-rays. Each protocol was terminated by a final local top-up dose (25 kV X-rays) of 5 Gy. The frequency of complete local denudation within the test area was used as the quantal end point. The kinetics of repair of sublethal damage was studied by snout irradiation with four equally spaced fractions, delivered at intervals of 35, 60, 90, 480 or 540 min, again followed by a local top-up dose of 5 Gy. The linear-quadratic model gave a satisfactory fit to the data with the exception of the four fraction/30-h data, suggesting cell cycle effects in this schedule. Analysis of the results with different two-step methods and with direct analysis yielded similar results. The alpha/beta ratio was determined to be approximately 11 GY (direct analysis: 11.6 Gy with 95% confidence limits of 8.1 and 16.4 Gy) and T1/2 was found to be 46 min (35-69 min). Both these values are in the range described for other acutely responding rodent tissues.

Animals↗
PubMed1993

Response of mouse tongue epithelium to single doses of bleomycin and radiation.

Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED50) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effect curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation.

Animals↗
PubMed1993

Endogenous factors modulating urinary bladder compliance in mice.

The application of repeated cystometric measurements in longitudinal long-term studies both in patients and experimental animals requires detailed knowledge of factors causing intraindividual variability. In the present study, the effect of age, body weight, estrus cycle phase, rectal temperature and premeasurement bladder volume on the results of cystometry in mice have been assessed. No systematic changes in bladder compliance parameters were observed with age (75 to 344 days) or body weight (18 to 38 gm.). Also, the animal's position in the estrus cycle had no effect on bladder capacity. The abdominal temperature, adjusted to 32 to 37.3C under anesthesia, did not affect the outcome of cystometry either. When the bladder was emptied at 1.5 to 3.5 hours before cystometry, a significant drop in bladder capacity to about 60% of individual control values was observed. This initial emptying clearly decreased the intraindividual variability in absolute terms (standard deviation), but not the relative variability (coefficient of variance). Thus only a shift in absolute values, but no improvement in reproducibility of cystometric results, could be achieved. Bladder filling to 10 or 25 mm. Hg 40 minutes to 2 hours before cystometry increased the bladder capacity to 120 or 145%, respectively, when anesthesia was maintained throughout the experiment. When intervals longer than 2 hours were studied, animals were allowed to regain consciousness between initial bladder filling and cystometry. Under these conditions, the capacity data returned to normal or subnormal values.

Aging↗
PubMed1992

Cystometry in mice--influence of bladder filling rate and circadian variations in bladder compliance.

Meaningful interpretation of cystometric measurements in experimental animals requires detailed analysis of factors that could affect the results. In the present study, the effect of catheter size and bladder filling rate were studied in detail; in addition, the influence of (day) time on bladder compliance was assessed by cystometry in mice. Bladder reservoir function was independent of the catheter size, when i.v. cannulae with outer diameters of 0.6 and 0.8 mm. were used, but leakage pressure and leakage volume were increased with the larger catheter. Neither the storage capacity nor the bladder wall resistance showed dependence on filling rates above 0.1 ml./min. Below this rate, bladder capacity increased and wall resistance decreased with decreasing filling rate. Furthermore, leakage eventually occurred below 20 mm. Hg with the lower filling rates. Marked diurnal variations in bladder compliance and wall resistance were observed. Maximum storage capacity was observed at 7 p.m. and the reservoir function subsequently decreased to a plateau between 1 a.m. and 1 p.m.

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PubMed1992

Increased radiation tolerance of mouse tongue epithelium after local conditioning.

The effect of local stimulation on mitotic activity and radiation tolerance was studied in mouse tongue mucosa. Silver nitrate solution (0.5-20%) was used for local conditioning. The most effective protocol comprised three daily treatments (days 0-2), yielding a delayed increase in 24 h mitotic counts by about 30% on days 5-7. The stimulating effect was independent of silver nitrate concentration. Sham treatment with saline or anaesthesia alone clearly depressed mitotic activity on days 2-4 without any subsequent overshoot. Radiation treatment was initiated on day 5 after three daily treatments with 3% silver nitrate solution. A top-up technique was employed, consisting of fractionated irradiation (300 kV X-rays) of the whole snout, followed by graded local test doses (25 kV X-rays) to induce denudation in a confined area of the inferior tongue surface. Silver nitrate conditioning did not alter the radiosensitivity of the epithelium to single local doses, but shortened the latency to denudation from 11 to 8 days. In contrast, a clear increase in tolerance to fractionated irradiation, delivering 5 x 2.5, 5 x 3.5, 5 x 4.5 Gy or 3 x 5.2 Gy in 7 days, was observed, equivalent to about four, two, one and two extra dose fractions. This approach may be a suitable way to increase radiation tolerance of oral mucosa in clinical radiotherapy.

Animals↗
PubMed1992

Early changes in mouse urinary bladder function following fractionated X irradiation.

Functional changes in the mouse urinary bladder following single-dose or fractionated irradiation were assessed by cystometry, i.e., by measuring the intravesical volume-pressure relationship during transurethral filling. The early response presented as a dose-dependent and transitory decrease in the reservoir function of the organ as defined by the intravesical volume at a filling pressure of 10 or 20 mm Hg, V10 or V20. The quantal dose response used in the present study was a reduction in the individual bladder volume (V10 and V20) by at least 50%. After single doses greater than or equal to 10 Gy, the reaction occurred between Days 7 and 25 with maximum prevalence between Days 7 and 14. The individual duration of the response was 3-9 days. Treatment with single doses and 2, 3, 5, and 10 fractions demonstrated a significant sparing effect with ED50 values of 18.3, 24.9, 26.8, 29.8, and 38.0 Gy, respectively. The linear-quadratic model fitted the data reasonably well when tested according to Tucker (Int. J. Radiat. Oncol. Biol. Phys. 10, 1933-1939, 1984). The alpha/beta ratios estimated with different two-step techniques ranged from 11.1 to 12.4 Gy. Analysis of the data as proposed by Thames et al. (Int. J. Radiat. Biol. 49, 999-1009, 1986) yielded an alpha/beta value of 13.9 Gy (95% confidence limits 8.4 and 24.6 Gy), illustrating a fractionation effect typical for acutely responding tissues, although no clear cell depletion occurred in the urothelium.

Animals↗
PubMed1991

Proliferation kinetics of mouse tongue epithelium under normal conditions and following single dose irradiation.

Epithelial proliferation in the ventral surface of mouse tongue follows a pronounced circadian rhythm with a peak in mitotic activity at 10.00 a.m., preceded by a wave of DNA synthesis 8 h earlier. Nearly all cells (85%) pass through G2 and mitosis immediately after the S-phase; they subsequently divide again, usually after 2 or 3 days, indicating cohorts of cells with different G1-duration. The fraction of all nucleated cells comprised in one daily proliferation wave is about 20%, indicating a turnover time of the nucleated cell compartment of about 5 days. Cytotoxic injury by a single radiation dose of 20 Gy causes a steep decrease in cell counts, leading to complete denudation after 9-13 days. The difference between the latent period before ulceration and the tissue turnover time is explained by a marked proliferative activity of the doomed cells. The mitotic index increases steeply after day 1 to three times the control level, but most mitotic figures display gross abnormalities such as multipolar spindles or chromosome clumping. As a consequence cells with abnormal or multiple nuclei appear in the basal layers 3 days post irradiation and subsequently migrate to the upper layers. After denudation the epithelium rapidly becomes restored, with a phase of transient hyperplasia on days 13-14. Normal architecture is regained by day 15. Over the whole healing period the mitotic index remains at a high level, with most of the mitoses appearing histologically normal.

Animals↗
PubMed1990

Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses.

Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered.

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