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Biomedical subjects

C Streffer

Publications and source records attributed to C Streffer.

At least 145 records · Page 8Linked to original sources
PubMed1989

The vasculature of xenotransplanted human melanomas and sarcomas on nude mice. I. Vascular corrosion casting studies.

The vascular system of xenotransplanted human melanomas and sarcomas on nude mice was studied by means of microorrosion casting. In summary, the vascular system of xenotransplants can be described in termes of a simply structured system, lacking not only a hierarchy with respect to wall formation but also to vascular distribution. Thus, the vasculature clearly differs from that in normal tissues.

Animals↗
PubMed1989

The vasculature of xenotransplanted human melanomas and sarcomas on nude mice. II. Scanning and transmission electron microscopic studies.

The tumor-inherent vasculature plays a major role with respect to tumor sensitivity to ionizing radiation. Ultrastructural studies of the tumor vasculature are necessary in order to obtain more detailed information on the architecture and structure and on the sites affected by tumor therapy. The vasculature of xenotransplanted human tumors on nude mice was investigated in this study by means of scanning and transmission electron microscopy. Structurally complete, real arteries or veins are neither to be seen in the periphery nor in the center. Large-caliber vessels basically have a capillary wall structure. The endothelial cells show a very alternating height and electron density. Frequently, different cell types and tumor cells themselves are apparently involved in the formation of the vessel wall. The endothelium is characterized by very simple, immature cell contacts. In some tumors, the amount of vessels without or with incomplete endothelium seems to be higher than the number of structurally real capillaries. This has consequences as well for radiotherapy as for hyperthermia and chemotherapy.

Animals↗
PubMed1989

Analysis of structural and numerical chromosomal aberrations at the first and second mitosis after X irradiation of two-cell mouse embryos.

Two-cell mouse embryos were X-irradiated in the late G2 phase in vivo. The first and second postradiation mitoses were analyzed for chromosomal anomalies. The majority of structural aberrations visible at the first mitosis after irradiation were chromatid breaks and chromatid gaps; only a few interchanges and dicentrics were observed. The aberration frequency resulted in a dose-effect relationship which was well described by a linear model. At the second mitosis 29% of the structural aberrations of the first mitosis were counted; the aberration quality changed only slightly. It is discussed whether these aberrations are to be considered "new," "derived," or unchanged transmitted aberrations. Contrary to the results obtained after irradiation of one-cell embryos, little chromosome loss was induced by radiation in two-cell embryos.

Animals↗
PubMed1988

Prenatal death and malformations after irradiation of mouse zygotes with neutrons or X-rays.

Female mice (strain: "Heiligenberger Stamm") were irradiated with neutrons (7 MeV) or X-rays when embryos were at the early zygote stage; uterine contents were examined on gestation day 19 for prenatal mortality and malformed fetuses. For both radiation qualities, the dose-dependent survival curve fitted well to a simple exponential equation; the neutron relative biological efficiency (RBE) value was 2.3. The major fraction of deaths induced by exposure to neutrons or X-rays occurred before implantation. Aside from dead embryos, malformed fetuses were observed 19 days p.c. (postconception). The number of malformed fetuses increased with a linear-quadratic function of neutron or X-ray dose. Malformations were mainly gastroschisis, although omphaloceles and anencephalies were also observed. The neutron RBE value for the induction of malformations varied from 2.0 to 2.8 in the dose range tested. Except after 75-cGy neutrons, no significant increase in the proportion of stunted or skeletally malformed fetuses was noted. Our results indicated that the reaction of preimplantation embryos to irradiation could be more complex than the simple "all-or-none" response considered so far.

Abnormalities, Radiation-Induced↗
PubMed1988

Growth, cell proliferation and morphological alterations of a mouse mammary carcinoma after exposure to X-rays and hyperthermia.

A C57 mouse mammary carcinoma was irradiated with 10, 20 or 30 Gy of X-rays or heated to 43 degrees C for 30 min preceded or not by exposure to 10 Gy. Tumour growth, cell proliferation kinetics, induction of micronuclei and morphological changes in necrosis and vascular density were simultaneously determined. Treatment with radiation and/or hyperthermia produced only a delay in tumour growth of between 1 and 3.8 days. However, the effects of the treatments became more apparent when the amounts of muscle and necrosis were deducted from the originally measured tumour volume. Radiation-induced G2 block of the cells was observed at 12 h after irradiation alone. After the combined treatment, however, the G2 block was delayed beyond 12 h. Moreover, 24 h after the various treatments, the proportion of S-phase cells decreased considerably although the formation of micronuclei showed only a marginal increase. However, the ratio of S-phase cells to micronuclei was significantly reduced during this period. Whereas the amount of necrosis was markedly enhanced 5 days following treatment with 10 Gy plus heat, as well as after 30 Gy, no alterations in the density of small blood vessels could be observed during this period. These results clearly demonstrate that the apparent changes in tumour volume after X-rays and hyperthermia do not truly reflect the response of the constituent cells and that there are many other factors, for instance cell proliferation and morphological alterations, that influence the effects of radiation and hyperthermia on tumours.

Adenocarcinoma↗
PubMed1988

Aspects of metabolic change after hyperthermia.

Hyperthermia induces conformational changes of macromolecular structures. Such effects lead to a sudden inhibition of DNA, RNA and protein synthesis and a breakdown of membranes and of the cytoskeleton. These alterations can be very important for the mechanism of cell killing by hyperthermia. Furthermore hyperthermia induces a number of immediate metabolic changes by increasing metabolic rates. These alterations have been studied especially in intermediary metabolism like glycolysis, citrate cycle, lipid metabolism and oxidative phosphorylation. An increased turnover of ATP has been observed in cells and tissues during heating. These changes lead to a depletion of energy reservoirs. Also, disregulations occur at certain metabolic key points. Thus, the pathway of pyruvate into the citrate cycle via acetyl-CoA is apparently reduced in heated melanoma cells in vitro. The redox ratios of lactate/pyruvate, NADH/NAD+ and others are decreased. When the same melanoma cells are grown as a xenograft on nude mice the metabolic rates are also enhanced; however, the lactate/pyruvate ratio increases during a localized heating of the tumour. The extent of this effect is very variable in individual tumours and is apparently correlated with the blood flow. These alterations can be enhanced by glucose loading and can be used as an indicator of hypoxia within the tumour. Thus, the micromilieu can be modified by these metabolic effects in such a way that the thermosensitivity is increased. The data show that metabolic processes are directly and indirectly involved in cell killing by hyperthermia.

Animals↗
PubMed1988

Glutathione level in melanoma cells and tissue.

We studied the effects of hyperthermia by measuring the content of reduced (GSH) and oxidized (GSSG) glutathione separately in two human melanoma cell lines (MeWo, Be 11) and the xenografts of the same melanomas on nu+/nu+ mice. The Be 11 cell lines are less radiosensitive but more thermosensitive than MeWo cells. Therefore the levels of glutathione were also studied in Be 11 cells after combined treatment with 3.7 Gy plus 42 degrees C for 3 h. The levels of GSH were lower in both untreated MeWo cells and MeWo tumour than in Be 11 cells and Be 11 xenograft. After heating the cells in vitro at 42 degrees C for 3 h and the tumour for 30 min at 43 degrees C the levels of GSH and of GSSG increased in both melanoma cell lines. In the MeWo and Be 11 tumours hyperthermia did not markedly influence GSH levels but the GSSG levels decreased. From these data it followed that the ratios of GSH to GSSG were decreased in both cell lines, whereas the ratios increased in both tumours. X-irradiation had no significant effects on GSH level in Be 11 cell lines, but the content of GSSG increased markedly after combined treatment.

Animals↗
PubMed1988

Time factors in combined exposures of mouse embryos to radiation and mercury.

There are situations in which the exposure to more than one agent results in an enhanced risk for the exposed organism, that is in which the observed effect exceeds the effect expected from the addition of the individual effects. Our knowledge of such hazards is rather limited, in particular for those agents that occur in the environment of man. When early mouse embryos in vitro were exposed to ionizing radiation and mercuric chloride, the observed risk was higher than expected from the individual effects. This increase in risk was due to an interaction between mechanisms induced by ionizing radiation and mercury. To gain some more insight into the mode of interaction, the time requirements of mercury exposure were studied. The amount of interaction did not depend on mercury exposure before or during irradiation. However, to achieve an enhanced risk, exposure had to start as soon as possible after irradiation and had to last as long as possible. This time dependence suggests that if inhibition of DNA-repair is involved in the mechanism of interaction at all, then there must be an additional late process that is also impaired by mercury.

Animals↗
PubMed1988

Analysis of structural and numerical chromosomal anomalies at the first, second, and third mitosis after irradiation of one-cell mouse embryos with X-rays or neutrons.

One-cell mouse embryos were irradiated with X-rays or neutrons. Analysis of the first, second, and third postradiation mitoses revealed that the yields of structural aberrations increased linearly after exposure to both radiation qualities. For X-rays the aberration frequency decreased from the first to the third mitosis, whereas after neutrons it decreased from the first to the second mitosis but then increased in the third mitosis. RBEs of 4.7, 4.8, and 7.4 were calculated for the corresponding mitoses. It was clearly demonstrated that new aberrations were produced after the first postradiation mitosis and expressed during the second and third mitosis. Chromosome loss also increased with increasing radiation dose at the second mitosis. An RBE of 2 was calculated for this effect. Comparing the presented data with previous investigations on embryonic and fetal death after prenatal irradiation, it was concluded that the high radiosensitivity of the one-cell embryo is due to the induction of structural as well as of numerical chromosome aberrations.

Animals↗
PubMed1988

The one-cell mouse embryo: cell cycle-dependent radiosensitivity and development of chromosomal anomalies in postradiation cell cycles.

One-cell mouse embryos were irradiated with X-rays at different cell cycle stages. Examination of structural chromosomal anomalies and of micronucleus formation in postradiation mitoses and interphases demonstrated cell cycle-dependent radiosensitivities in the order: late G2 phase greater than G1 phase greater than S phase greater than early G2 phase greater than stage of decondensing nuclei. Comparison of the quality and quantity of chromosomal aberrations from the first to the third mitosis led to the conclusion that new chromosomal anomalies were formed in the course of postirradiation cell cycles. This hypothesis was supported by an increasing number of micronuclei from 24 to 48 h post-conception. In addition to structural chromosomal aberrations, radiation-induced chromosome loss was observed with a frequency that was obviously independent of the exposed cell cycle phase. Loss of acentric chromosome fragments and of single chromosomes contributed to the micronucleus formation.

Animals↗