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Biomedical subjects

J H Hendry

Publications and source records attributed to J H Hendry.

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

The radiosensitivity of kidney colony-forming cells: a short-term assay in situ in the mouse.

A short-term colony assay for renal tubule epithelium has been developed. Uranyl nitrate (UN) is a heavy metal nephrotoxin that induces acute tubule necrosis followed by a large compensatory increase in the rate of cell proliferation in the nephron. UN was used to precipitate latent damage following renal irradiation. Using a subcapsular colony count at 14 days after unilateral irradiation, a single-dose cell survival curve was obtained with a D0 of 4.2 +/- 0.3 Gy. High-dose irradiation of an exteriorized kidney resulted in a survival curve which was biphasic, with a plateau in survival between 18 and 40 Gy. Subtraction of this plateau level from all the survival data gave D0 values of 2.5 +/- 0.2 Gy (data analyzed between 7.5 and 16 Gy) or 2.0 +/- 0.2 Gy (over range 12-16 Gy). The D0 value obtained at 20 months after bilateral (or unilateral) kidney irradiation, without the use of UN, was 2.9 +/- 1.1 Gy (over range 10-14 Gy).

Colony-Forming Units Assay↗
PubMed1989

The response of murine intestinal crypts to short-range promethium-147 beta irradiation: deductions concerning clonogenic cell numbers and positions.

An exteriorized loop of mouse intestine was exposed to 147Pm low-energy electrons, where the dose rate decreased by a factor of 5 from the base of the crypt to the top of the proliferative zone. A crypt survival curve was obtained, expressed in terms of exposure time. The shape of the curve was interpreted in terms of survival parameters for colony-forming cells (clonogens) derived using 137Cs gamma rays and the depth-dose curve measured for 147Pm electrons. It is concluded that the shape of the crypt survival curve using 147Pm electrons is inconsistent with the notion of either the presence of a large number of clonogens or a small number near the top of the proliferative zone. A computer fitting procedure showed that the best agreement between predicted and observed curves was achieved with 2.7 +/- 0.5 clonogens at cell position 5.6 +/- 0.6, in the putative stem-cell zone.

Animals↗
PubMed1988

An autoradiographic study of the intrarenal localisation and retention of cisplatin, iproplatin and paraplatin.

The intrarenal localisation of platinum following the intravenous administration of platinum-195m-labelled cisplatin, iproplatin and paraplatin was studied using autoradiography. Following injection of cisplatin, platinum was distributed throughout the kidney even up to 14 days after treatment. In the case of iproplatin and paraplatin rapid platinum clearance was noted from the glomeruli, blood vessels and renal medulla within 2 h of administration. Relative cortical and medullary platinum radionuclide concentrations for all three agents were determined by Chalkley grid analysis. This showed greater relative concentrations of platinum in the cortex at increasing times following iproplatin and paraplatin compared with cisplatin. It is suggested that the lower renal toxicity of iproplatin and paraplatin than of cisplatin may be due to reduced platinum retention within the pars recta.

Animals↗
PubMed1988

Lack of protection by oestrogen from radiation-induced testicular damage in the rat.

The influence of pretreatment with oestradiol dipropionate (E) on the response of the rat testis to radiation has been studied. Treatment of rats for 3 weeks with E (100 mg/kg per week) induced severe atrophy of the testis. At this time, the testes were locally irradiated to doses of 0, 4 or 15 Gy, E treatment was continued for a further week and the rats were killed 24 or 36 weeks later. Radiation alone had a marked effect on spermatogenesis as assessed by testicular weight and counts of regenerating tubule cross-sections. At 24 weeks, 8% of cross-sections were found to possess spermatogenic cells after 4 Gy and this had increased to 15% at 36 weeks. No significant regeneration was observed after 15 Gy. Similar results were obtained in those rats pretreated with E. Following irradiation alone, decreases in interstitial cell numbers and testicular luteinizing hormone (LH) receptors reflected Leydig cell damage. Again, pretreatment with oestrogen did not appear to reduce Leydig cell damage. The results of the present study suggest that pretreatment with oestrogen is not able to reduce the testicular damage induced by moderate to high single doses of radiation.

Animals↗
PubMed1988

Re-irradiation of mouse skin: similarity of dose reductions for healing and macrocolony endpoints.

The amount of residual injury in mouse tail skin, assessed by the decrease in re-irradiation dose for equal effect, was similar whether assessed using healing or colony endpoints (17-21% after single priming doses). There were tendencies towards an increased sensitivity of the colony-forming cells by a factor of about 2, and less residual injury after multifractionated priming doses. These observations are compatible with a lower alpha/beta ratio characterising the response to dose fractionation for residual injury than for the acute healing response.

Animals↗
PubMed1988

Residual skin injury after repeated irradiation: differences observed using healing, macrocolony, and microcolony endpoints.

Following three repeated tolerance doses to mouse tail skin, residual injury was characterized by a 35% reduction in the iso-effective dose compared to age-matched controls, using healing or macrocolony endpoints. In contrast, the reduction was only 9%, measured using microcolony formation. The colony data showed that the reduction was a constant dose, not a dose-modifying effect. The residual injury is interpreted as due to a reduced density of microcolony-forming cells in the epidermis, and these are less capable of macrocolony formation and hence of re-epithelialization in the repeatedly-irradiated epidermis.

Animals↗
PubMed1988

Survival of cells in mammalian tissues after low doses of irradiation: a short review.

A survey of data in the literature indicates that the radiosensitivity of cells to doses less than 1 Gy varies widely within cell lineages and less so between lineages. This is due in large part to the differentiation status and division capacities of the cells, and possibly also to the grouping of cells into 'viable units'. In addition, the mode of cell death is important, and cells susceptible to natural apoptosis are particularly radiosensitive. There are also quite marked differences in cell sensitivity between species.

Animals↗
PubMed1988

The doubling time of regenerating clonogenic cells in the crypts of the irradiated mouse small intestine.

The number of clonogenic cells per intestinal crypt has been estimated in control and gamma-irradiated mice, from the response to a single or two test doses. Control unirradiated mice contained 43 +/- 8 clonogenic cells per crypt, which was reduced to about 3 per crypt immediately after 8.0 Gy. After a mitotic delay which was approximately 18 h or 2.25 h/Gy the number of clonogenic cells per crypt increased exponentially with a doubling time of 21 +/- 4 h to reach the control values by about the 4th day postirradiation. The growth curve was related to the changes in total cellularity and the cell production rate per crypt. Since both of these rise during the period of clonogenic regrowth some clonogenic cells must be diverted into the dividing transit cell population, so that the cell cycle time will be shorter than the doubling time given above.

Animals↗
PubMed1988

Persistent dose-dependent increases in cycling of haemopoietic precursor cells after irradiation.

Between 3 weeks and 36 months after irradiation of mice, there was a dose-dependent increased level of cycling in haemopoietic stem cells (CFU-S) and in granulocyte-macrophage precursor cells (GM-CFC). For CFU-S the percentage kill measured using the thymidine suicide technique increased from about 10% in controls to a high and persistent average level of about 45% after 10 Gy gamma-rays, and for GM-CFC the increase was from about 30% to about 50%.

Animals↗
PubMed1988

Long-term haemopoietic injury in mice after repeated irradiation: precursor-cell cycling and its regulation.

The cycling rate of haemopoietic stem cells (day 9 CFU-S) and granulocyte-macrophage colony forming cells (GM-CFC) in mouse femora was, in response to reduced numbers, elevated at all times of sampling between 3 weeks and 10 months after 4 repeated doses of 4.5 Gy X-rays (3 wk between doses). The level of a stimulator of CFU-S cycling was also elevated, and this was observed in both axial and marginal regions of the marrow inside the shaft. However, the rate of production of the stimulator was low; lower than previously reported in marrow regenerating after a single dose of 4.5 Gy, indicating damage to the regulatory stromal cells. The distribution of CFU-S across the axial and marginal zones of femoral marrow was changed from that in normal mice, where higher concentrations were found near the bone surface, to a more uniform distribution.

Animals↗
PubMed1988

The effect of low dose rate on recovery of hemopoietic and stromal progenitor cells in gamma-irradiated mouse bone marrow.

Long-term recovery of mouse hemopoietic stem cells (CFU-S and CFU-S per colony), granulocyte-macrophage precursor cells (GM-CFC), and stromal colony-forming units (CFU-F) after doses up to 12.5 Gy was almost complete by 1 year when the dose rate was reduced to 0.0005 Gy/min compared to incomplete recovery after doses up to only 6.5 Gy given at greater than 0.7 Gy/min. This sparing effect of dose rate on long-term hemopoietic recovery is in contrast to the generally reported lack of dependence on dose rate for acute survival of hemopoietic progenitors after doses up to 5 Gy. The present results are compatible with the hypothesis that good recovery of the stroma should be reflected in the long-term recovery of hemopoiesis.

Animals↗
PubMed1988

Long-term repair in vivo of colony-forming ability and chromosomal injury in X-irradiated mouse hepatocytes.

The radiosensitivity of mouse hepatocytes in vivo was measured in terms of clonogenicity or chromosome damage (micronucleus production). Within 24 h of irradiation there was a dose-dependent increase in clonogenicity (dose-modifying factor, DMF = 1.37 +/- 0.09) followed by long-term repair which resulted in a DMF of 3.49 +/- 0.23 at 11 months. Such repair also took place, but to a lesser extent, after the end of fractionated irradiation. Cell proliferation, measured by tritiated thymidine autoradiography, was insufficient to explain the long-term reduction in radiosensitivity in terms of a dose-dependent replacement of damaged cells. Although there was a reduction in the frequency of cells with micronuclei, postirradiation, the magnitude of this decrease was relatively small; the DMF for micronucleus-free cells at 11 months was only 1.49 +/- 0.25. Thus the long-term increase in clonogenicity can only partially be explained in terms of repair of chromosome injury, assessed by the production of micronuclei.

Animals↗
PubMed1988

Dose fractionation and hepatocyte clonogens: alpha/beta congruent to 1-2 Gy, and beta decreases with increasing delay before assay.

The sensitivity to X-ray dose fractionation was assessed for hepatocytes forming colonies in fat pads in mice. When the cells were assayed 1 day after the last irradiation the alpha/beta ratio was 1.0-1.6 depending on the method of analysis. The alpha/beta ratio describing the shape of the single-dose survival curve was much higher, and it did not predict the response to fractionation. When the assay was delayed for 10 months after the fractionated irradiation, the alpha/beta ratio was 1.9-2.1, and the beta component showed the greatest change with time. It is concluded that hepatocytes respond to dose fractionation in a manner expected of a late-responding tissue, even when the cells are assayed as early as 1 day after the last dose.

Animals↗
PubMed1987

Estimates of the number of clonogenic cells in crypts of murine small intestine.

There is a proliferative cell hierarchy in the mouse intestinal crypt with ancestral stem cells which can regenerate all components of the lineage after injury (clonogenic cells). The number of these clonogenic or regenerative cells per crypt can be estimated from radiobiological experiments where doses of radiation are used to kill cells and ablate crypts. Various approaches can be adopted which provide different estimates of this number of cells. One of the conventional approaches used in the past provided estimates of about 70-80 clonogenic cells per crypt (i.e. about 50% of the proliferative or 30% of all crypt cells). A technically simpler approach has recently been suggested. This has been used here to provide many independent estimates of the number of crypt clonogenic cells. These suggest about 32 clonogenic cells exist per crypt i.e. about half the previous estimate and about twice the number of putative "functional" stem cells (those which operate as stem cells in the normal steady-state crypt). The reasons for the differences are discussed. The new estimates are compatible with the hypothesis that the crypt contains a ring of about 16 functional stem cells which are expected to be clonogenic, besides which there is a second ring of 16 clonogenic cells which represent early transit cells (the immediate daughters of the stem cells) which can act as clonogenic cells if required after radiation injury.

Age Factors↗
PubMed1987

The radiation sensitivity of the haemopoietic microenvironment--effect of dose rate on ectopic ossicle formation.

The haemopoietic microenvironment (HM) consists of a complex mixture of cellular types and extra-cellular matrix. It is essential for prolonged haemopoiesis in both the normal situation and after bone marrow transplantation. The competence of the HM can be assessed by ectopic grafting of femoral marrow. A complete haemopoietic organ develops at the site of implantation. Stem cells (CFU-S) which inhabit the ossicle formed after ectopic implantation can be measured, to assess the function of the engrafted HM to support haemopoiesis. Using this functional endpoint we have examined the radiation sensitivity of the HM at both high and low dose rates, and conclude that high doses of gamma-irradiation delivered at 4 Gy/min or 0.016 Gy/min have widely different effects on the HM, the former proving much more damaging than the latter.

Animals↗
PubMed1987

Lack of differential sparing of late ischaemic atrophy and early epidermal healing, after dose fractionation of mouse tails down to 2.6 Gy per fraction.

Long-term atrophy of irradiated mouse tails began after about 5 months, and the incidence rose steadily to the end of the lifespan. The major associated histological change was atherosclerosis in the single tail artery. The incidence of the ischaemic atrophy was dependent on the size of the irradiated volume. The probability of ischaemic atrophy assessed at 3 years after irradiation was little dependent on the dose. The fractionation effect was described by alpha/beta congruent to 30 Gy, which was not lower than the range of values applicable for healing of the early epidermal reactions on the tail. Hence the general finding of a sparing of late effects in tissues using low doses per fraction was not observed in these experiments using dose fractions down to 2.6 Gy and the present endpoints.

Animals↗