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Biomedical subjects

J Haveman

Publications and source records attributed to J Haveman.

At least 73 records · Page 4Linked to original sources
PubMed1983

Influence of pH and thermotolerance on the enhancement of X-ray induced inactivation of cultured mammalian cells by hyperthermia.

The influence of pH and thermotolerance on thermal enhancement of radiation effects have been studied with M8013 cells, derived from a transplantable murine mammary carcinoma. The effect of combined heat-irradiation treatment of cells at different pH of the medium clearly shows an influence of the pH. Thermal enhancement of the effectiveness of radiation is relatively strong below pH 7.0 and above pH 7.75. In the physiological range pH 6.7-7.4 the influence of pH is not very large. This implies that combination of hyperthermia and radiotherapy in cancer treatment would not give much therapeutic advantage from low pH which is often observed in solid tumours as this low pH is rarely below pH 6.7. Sensitization of cells to the effects of heat treatment alone at a low pH of the cellular medium is greatly decreased when thermotolerance is induced in the cells by a prior heat treatment 4-6 hours before the final treatment. When the cells are in the thermotolerant state, induced by a prior heat treatment, not only resistance to heat treatment, but also resistance to combined heat-irradiation treatment is observed. The degree of this latter resistance is independent of the pH of the cellular medium during the combined heat-irradiation treatment. In spite of the resistance, strong thermal enhancement of radiation effects can be observed when cells are treated in the thermotolerant state by a strong heat treatment. Without thermotolerance such a strong heat treatment, whether combined with irradiation or not, caused so much effect that it was impossible to determine relative cellular survival. The enhancement of radiation effects by a strong heat treatment with cells in the thermotolerant state is largely independent of the pH of the cellular medium.

Adaptation, Physiological↗
PubMed1983

The response of previously irradiated mouse skin to heat alone or combined with irradiation: influence of thermotolerance.

The skin of the mouse foot was used to study the effects of previous irradiation on the response to hyperthermia (44 degrees C), to irradiation, or to irradiation combined with hyperthermia (43 degrees C or 44 degrees C). Hyperthermia was applied by immersing the mouse foot into a hot waterbath and irradiation was performed using a 250 kV X-ray generator. Previous irradiation of the feet of mice 90 days before, with 20 Gy, increased the subsequent response to heat alone, or when combined with irradiation, as well as to irradiation alone. It had little effect on the thermal enhancement ratio's for both acute and late skin reactions. Memory of the previous irradiation treatment could be masked when the temperature of the subsequent heat treatment alone, or when combined with irradiation, was 44 degrees C. A priming heat treatment induced resistance both to a subsequent heat treatment and to a subsequent combined irradiation-heat treatment in normal skin as well in previously irradiated skin. This 'resistance' is probably mainly the result of thermotolerance induced in cells in the skin by the priming heat treatment. In thermotolerant skin a 'memory' of the previous irradiation was always evident when the reaction after heat alone or heat combined with irradiation was measured. When the late skin reaction was considered, a larger 'memory' of the previous irradiation treatment was always evident, compared to the acute skin reaction: the 'remembered' dose in the late skin reaction was about two times the 'remembered dose' in the acute skin reaction.

Acclimatization↗
PubMed1982

Effect of hyperthermia and misonidazole on the radiosensitivity of a transplantable murine tumor: influence of factors modifying the fraction of hypoxic cells.

Hypoxia has been demonstrated to play an important role in the effect of hyperthermia on tumors. We have studied the influence of different factors modifying the oxygenation status of a transplantable murine mammary adenocarcinoma (tumor volume and pentobarbital sodium anesthesia). The effect of hyperthermia alone on the tumor is not significantly influenced by the change in oxygenation status during the growth of the tumor. Also, the large increase of the acutely hypoxic cell fraction, as a result of anesthesia, does not change the effect of hyperthermia alone. In the combined irradiation-heat treatment there is a clear influence of the chronically hypoxic cell fraction on the response to hyperthermia: an increase in tumor size, resulting in a larger hypoxic cell fraction, leads to an increase in thermal enhancement ratio. However, the increased acutely hypoxic cell fraction, resulting from anesthesia, did not lead to an increase in thermal enhancement ratio; in fact the enhancement ratio apparently decreased. In spite of the fact that hyperthermia was applied immediately after irradiation no potentiation of radiation effects was found. The thermal enhancement of the radiation response was never larger than the enhancement as a result of misonidazole. All thermal enhancement could be explained by effects of heat on the chronically hypoxic cell fraction. Misonidazole had no effect on the response of tumors to heat alone, but greatly enhanced the effect of heat combined with irradiation. Anesthesia of the animals did not influence these effects of misonidazole.

Anesthesia↗
PubMed1982

Effects of irradiation by single or multiple fractions per day on transplantable murine mammary carcinoma.

Effects of different fractionation schedules of irradiation were studied in an experimental mammary adenocarcinoma transplanted in the back of mice. The number of fractions per day varied from one to three, keeping the daily dose constant. It was found that an increase of the number of fractions per day did not necessarily lead to a decrease in the tumour response, as might be expected for the same total dose. At a twelve-day overall time, three fractions per day did not give such a good result as one fraction per day, but at a nineteen-day overall time three fractions per day were about as good as one fraction per day; and below 45 Gy total dose, the result with three fractions per day even seemed to be better. The effects of actinomycin D administered during the irradiation treatment show that schedules with three fractions per day possibly take better advantage of repair of sublethal and potentially lethal damage than schedules with one fraction per day. Administration of misonidazole during the irradiation treatment led to a dose-modifying effect of 1.2 in one fraction per day schedules but had no significant effect in three fractions per day schedules. The present results may provide guidelines for clinical application of irradiation schedules with more than one fraction per day.

Adenocarcinoma↗
PubMed1981

The role of energy in hyperthermia-induced mammalian cell inactivation: a study of the effects of glucose starvation and an uncoupler of oxidative phosphorylation.

When cultured Chinese hamster cells were exposed to 43 degrees C hyperthermia, effects due to glucose deprivation and to the presence of the uncoupler of oxidative phosphorylation, carbonylcyanide-3-chlorophenylhydrazone, during the 43 degrees C treatment proved to be strongly accelerated compared to the effects at normal temperature (37 degrees C). This strongly indicates that the availability of energy plays an important role in the response of these cells to hyperthermia. One of the reasons cells die after hyperthermia may be a lethal lack of energy. Cells heated before glucose deprivation were able to maintain viability for a longer period during deprivation than cells without the preheat treatment. As the cells might develop thermotolerance after the heat exposure, this suggests that cells in the thermotolerant state use energy in a more economical way.

Animals↗
PubMed1981

Radiosensitivity of microscopic tumours of a transplantable mammary adenocarcinoma in mice.

Evidence is presented that microscopic tumours (of a transplantable murine mammary carcinoma, M8013X) grow faster than larger, palpable, tumours. Microscopic tumours are also more radiosensitive than larger tumours. The decrease in radiosensitivity in larger tumours is prevented to a large extent by misonidazole, which has no significant effect on the radiosensitivity of microscopic tumours. The retardation in growth rate which occurs after the fast microscopic growth is probably related to the appearance of hypoxic cells. Both the decrease in growth rate and the progressive development of hypoxia may be caused by the relatively poorer blood flow in larger tumours. Part of the radioresistance in "large" tumours ( approximately 250 mm3) seems to be due to factors other than hypoxia; maybe cell-kinetic factors also play a role. The intrinsic radiosensitivity of tumour cells in microscopic tumours was assessed by means of a modified latency test: the Dq and Do were 2.2 and 2.5 Gy respectively. A number of factors which may influence the reliability of these estimates are discussed.

Adenocarcinoma↗
PubMed1980

The capacity of lysosomes of cultured mammalian cells to accumulate acridine orange is destroyed aby hyperthermia.

Lysosomes of cultured mammalian cells, derived from a transplantable murine mammary adenocarcinoma, irreversibly lose their capacity to accumulate the fluorescent dye acridine orange after hyperthermia. As acridine orange may be regaraded as a fluorescent probe of the internal pH of the lysosomes, we may conclude that the ability of lysosomes to maintain a low internal pH is destroyed by hyperthermia. The effects of hyperthermia on lysosome fluorescence and on cell survival show several similarities: in both cases hyperthermia is more effective at low pH, below pH 7.0, and CCP (carbonylcyanide-m-chlorophenylhydrazone) enhances effects at low pH, but has no clear effect at pH 8.0. This leads to the conclusion that effects on lysosomes are an important and early event in cellular injury caused by hyperthermia. The activation energy, however, obtained for the effects of hyperthermia on lysosome fluorecence is about a factor of two lower athan the activation energy reported for cell survival after hyperthermia. This suggests that the effect on lysosomes is not directly caused by hyperthermia but is triggered by some other hyperthermia-induced cellular damage.

Acridine Orange↗
PubMed1980

The influence of pH on the survival after X-irradiation of cultured malignant cells. Effects of carbonylcyanide-3-chlorophenylhydrazone.

Irradiation of cultured murine mammary carcinoma (M 8013 S) cells during incubation in buffers of different pH showed a decrease in radiation sensitivity with lower pH. The presence of CCCP (carbonylcyanide-3-chlorophenylhydrazone) during incubation had no effect at pH values above 7.5, but at lower pH there was a marked increase in radiation sensitivity. The effects of CCCP are presumably related to its proton-conducting properties.

Animals↗
PubMed1976

Flash-induced absorption changes of the primary donor of photosystem II at 820 nm in chloroplasts inhibited by low pH or tris-treatment.

A comparative study is made, at 15 degrees C, of flash-induced absorption changes around 820 nm (attributed to the primary donors of Photosystems I and II) and 705 nm (Photosystem I only), in normal chloroplasts and in chloroplasts where O2 evolution was inhibited by low pH or by Tris-treatment. At pH 7.5, with untreated chloroplasts, the absorption changes around 820 nm are shown to be due to P-700 alone. Any contribution of the primary donor of Photosystem II should be in times shorter than 60 mus. When chloroplasts are inhibited at the donor side of Photosystem II by low pH, an additional absorption change at 820 nm appears with an amplitude which, at pH 4.0, is slightly higher than the signal due to oxidized P-700. This additional signal is attributed to the primary donor of Photosystem II. It decays (t 1/2 about 180 mus) mainly by back reaction with the primary acceptor and partly by reduction by another electron donor. Acid-washed chloroplasts resuspended at pH 7.5 still present the signal due to Photosystem II (t 1/2 about 120 mus). This shows that the acid inhibition of the first secondary donor of Photosystem II is irreversible. In Tris-treated chloroplasts, absorption changes at 820 nm due to the primary donor of Photosystem II are also observed, but to a lesser extent and only after some charge accumulation at the donor side. They decay with a half-time of 120 mus.

Chloroplasts↗
PubMed1976

Primary reactions of photosystem II at low pH. I. Prompt and delayed fluorescence.

Prompt and delayed chlorophyll fluorescence have been studied in broken spinach chloroplasts at pH values down to 2.6. No direct effect of low pH on the primary charge separation in Photosystem II was observed. The irreversible inactivation of a secondary electron donor in a narrow pH range around pH 4.5 was demonstrated. At lower pH values the photooxidized form of a more primary electron donor, revealed by its efficient fluorescence quenching, was reduced with a half time of about 200 mus, 25% by another electron donor and 75% by back reaction with the reduced acceptor. The electron donation had a half time of 800 mus and was practically irreversible. The back reaction had a pH dependent half time: about 270 mus at pH 4 and increasing towards lower pH. The competition of both reactions resulted in a net efficiency of the charge separation at pH 4 of 25%, increasing towards lower pH.

Chlorophyll↗
PubMed1975

Identification of the 120 mus phase in the decay of delayed fluorescence in spinach chloroplasts and subchloroplast particles as the intrinsic back reaction. The dependence of the level of this phase on the thylakoids internal pH.

After a 500 mus laser flash a 120 mus phase in the decay of delayed fluorescence is visible under a variety of circumstances in spinach chloroplasts and subchloroplast particles enriched in Photosystem II prepared by means of digitonin. The level of this phase is high in the case of inhibition of oxygen evolution at the donor side of Photosystem II. Comparison with the results of Babcock and Sauer (1975) Biochim. Bio-phys. Acta 376, 329-344, indicates that their EPR signal IIf which they suppose to be due to Z+, the oxidized first secondary donor of Photosystem II, is well correlated with a large amplitude of our 120 mus phase. We explain our 120 mus phase by the intrinsic back reaction of the excited reaction center in the presence of Z+, as predicted by Van Gorkom and Donze (1973) Photochem. Photobiol. 17, 333-342. The redox state of Z+ is dependent on the internal pH of the thylakoids. The results on the effect of pH in the mus region are compared with those obtained in the ms region.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗