Early and late radiation reactions in mouse feet.

The relationship between early and late radiation damage has been analysed by comparing the early skin reaction (desquamation in the first month) with the late foot deformity seen at 6 months, for mice from a wide variety of different fractionation experiments. A close correlation was observed between the early and late reactions in each experiment and the relationship was the same for all the experiments except for 17-64 fractions given over a short time. The fractionation schemes included single doses and 2-64 fractions, and the overall times ranged from 1 day to 6 months. This close correlation for such a wide variety of treatments suggests that the two end points are not necessarily independent responses of different tissues and that late damage in the mouse foot can result secondarily from depletion of the basal layer of the epidermis. Late foot deformity is therefore not a reliable model for the response of a slowly proliferating tissue

Endothelial proliferation in tumours and normal tissues: continuous labelling studies.

The proliferation rate of vascular endothelium has been studied using repeated administrations of tritiated thymidine, given every 8 h for 1 week. Five experimental mouse tumours have been investigated and compared with placenta and with normal tissues. The large difference in labelling indices between tumour and normal endothelium that has previously been detected with single injections of ([3H]dT) is confirmed by these continuous labelling studies. The potential doubling time of the tumour endothelium is estimated to be between 2.4 and 13 days for the five tumours. Tpot for the placenta is at least as short. The turnover time of the normal tissue endothelium is estimated to be 20-2000 times longer (47-23,000 days) and does not seem to differ in slow turnover tissues e.g. lung and liver from that in tissues where the parenchymal cells are rapidly turning over e.g. jejunum or skin

Endothelial-cell proliferation in experimental tumours.

The proliferation characteristics of vascular endothelium have been studied in 131 individual experimental tumours, representing 18 transplanted tumour lines. The labelling index (LI) is high in most tumours, with a mean value of 0.9%, regardless of the growth rate of the tumours, or whether different tumour types are considered or individual tumours from within one line are studied in detail. A similar high LI value has been found by others for a human tumour. These high LI values may even underestimate the proliferation in new capillary buds. The high proliferative index of tumour endothelium is in marked contrast with the previously reported low 3HTdR uptake into normal tissue blood vessels. It seems likely that it is the type of new vessels formed that will influence tumour growth rates more than the simple rate of endothelial-cell proliferation. The large difference between the proliferation characteristics of tumour endothelium and normal tissue endothelium, recently identified as a possible approach for tumour therapy, has now been confirmed for a range of animal tumours and a human tumour

Productie en kostprijs van pootvis (WP 4)

De cyclus van een marktwaardige consumptievis binnen de aquacultuur bestaat uit twee fases. De hatcheryfase, waar ouderdieren tot paaien worden gebracht en de nakomelingen tot pootvis worden gekweekt. En de doorgroeifase waar de pootvis wordt opgegroeid tot consumptievis. De prijs van deze consumptievis wordt mede bepaald door de kosten van de in eerste instantie ingekochte of voorgekweekte pootvis wat vaak een significant aandeel heeft in de kostprijsopbouw. De kostprijs van pootvis is opgebouwd uit verschillende soorten kosten. Alle factoren die van invloed zijn op de kweek van pootvis zijn in twee kostenposten te verdelen: lopende kosten en vaste kosten. Al deze kosten worden bepaald door biologische en technische invloeden vanuit het proces (mortaliteit, groeisnelheid, temperatuur etc.). Van een aantal vissoorten (zeebaars, Afrikaanse meerval) is de kostprijs en de kostprijsopbouw van pootvis bekend. Bij noorzee tong (Solea solea) is dit nog niet in kaart gebracht. Eerste pogingen gaan terug op berekeningen in de jaren 200 en 2001. Maar deze zijn niet publiek. Het is dus noodzakelijk om de kostprijs van tong pootvis te berekenen, om de haalbaarheid van tong kweek te onderbouwen

Interaction of radiosensitizers and WR-2721. I. Modification of skin radioprotection.

We have studied the radiomodifying action in mouse skin of WR-2721 and misonidazole (MISO) when used alone or in combination. The radioprotection with WR-2721 was drug-dose dependent and highly influenced by the O2 concentration at the time of irradiation. Significant sensitizaton was observed with MISO, especially in air-breathing mice. The combination of WR-2721 and MISO produced a radiation response intermediate between the resistant and sensitive responses to either drug alone. The precise degree of sensitivity was dependent on the relative doses of protector and sensitizer. We have also studied the interaction of both drugs in terms of drug-induced lethality, which showed a clear toxic interaction. The WR-2721 LD50 was reduced by a factor of 1.4 with only 200 mg/kg of MISO. We conclude that the combination of WR-2721 and MISO shows an interaction in terms of drug toxicity and radiation response, such that the radioprotection of skin is reduced or even abolished with low doses of MISO

Hyperthermia Treatment of Experimental Tumors

The therapeutic advantage of combining hyperthermia with x-irradiation to treat tumors depends on whether or not it is possible to achieve greater thermal sensitization of tumors than of normal tissues. To determine such therapeutic gain factors (TGE), we assessed the response of mouse skin and seven transplantable mouse tumors to graded x-ray doses given alone or combined with moderate heat (42.5°C for 60 minutes). We constructed dose response curves for the average early skin reaction and for the induced delay in tumor regrowth to an arbitrarily chosen size. We studied the following areas: 1) the therapeutic gain of combining heat with x-irradiation; 2) irradiation and heat sequencing; 3) vascular occlusion; 4) temperature uniformity; 5) hyperthermia and metastatic spread; 6) fractionated treatment; and 7) thermal tolerance. Our results are not as promising as those of other published studies. We have shown that the time interval between heat and irradiation is important, and we believe that the separate cytotoxic action of heat and x-irradiation is likely to be more beneficial than the synergistic effect of combining the two in close sequence. We have also demonstrated the deficiencies of using hot water to achieve uniform heating, and the possible artefacts of vascular occlusion. We observed no significant effect on the spread of metastases when heat is used adjunctively with x-rays. We also induced thermal tolerance in a mouse tumor, which may account for the loss of therapeutic advantage seen with fractionated treatments

Skin sensitization by misonidazole: a demonstration of uniform mild hypoxia.

Skin reactions on irradiated mouse feet were used to measure the radiosensitization of normal tissues by misonidazole (MISO). Fractionation schedules of 1, 2, 5 and 10 daily doses of X-rays were combined with either 100 mg/kg or 670 mg/kg MISO. When unanaesthetized mice were irradiated in air, significant sensitization was observed with both the high and low drug doses, in all fractionation schedules. There was no decrease in sensitization with fractionation, even using fractions as small as 5 Gy. This indicates that many of the cells in mouse skin may be marginally hypoxic, and that sensitization at low doses is possible. Irradiation in O2 without MISO rendered the skin more sensitive to X-rays than in air. MISO given 30 min before single doses of radiation further sensitized the skin, but for 10 fractions in O2 no MISO sensitization was detected. There was little evidence for cytotoxic killing in skin by MISO. Repair of radiation damage was slightly reduced when MISO was present, during or after irradiation