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J V Moore

Publications and source records attributed to J V Moore.

At least 91 records · Page 5Linked to original sources
PubMed1985

Lack of correlation between differentiation status and response to radiation of three murine squamous cell carcinomas.

The gross growth rate, histology, cellular kinetics, and in situ radiobiological response have been measured for three murine, keratinising squamous cell carcinomas that differed in their degree of differentiation. Growth rate was fastest in the least-differentiated tumour, slowest in the best-differentiated. However, the kinetics of the compartment of undifferentiated cells that are likely to be radiotherapeutically important, were the same for the three lines. There was no correlation between degree of differentiation and intrinsic or apparent radiosensitivity as measured by the growth delay assay. The radiobiologically best-oxygenated tumour was that which has the largest stromal component and this was not the best-differentiated tumour.

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PubMed1985

Differential effect of i.p.- and i.v.-injected adriamycin on the clonogenic spermatogonia of murine testis.

The response of murine clonogenic spermatogonia has been measured after intraperitoneal or intravenous injections of adriamycin (ADR). When measured over the whole testis, the survival curve for regenerating tubules after i.p. ADR had a 10-15% lower LD37 dose (that dose which sterilises 37% of tubules) but a two-fold higher average D0 for the clonogenic cells than that for i.v. ADR. Survival was then measured in concentric zones of these equatorial sections of testis. For i.v. injection survival parameters varied little between zones in the centre of the testis and zones adjoining the testicular capsule. In contrast, for i.p. ADR central zones had a 40% higher LD37 but the same D0 as for i.v. ADR, while peripheral zones had LD37s as little as 35% of the i.v. figure and mean D0s 2-3 times higher. Pharmacokinetic considerations that might lead to these differences in clonogenic response are discussed.

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PubMed1985

Tumour cords in 52 human bronchial and cervical squamous cell carcinomas: inferences for their cellular kinetics and radiobiology.

Tumour cords have been measured in 33 cases of squamous cell carcinoma (SCC) of the bronchus and 19 cases of SCC of the uterine cervix. The overall mean cord radius for SCC in both sites was 104 microns, similar to the overall mean for various tumours in rodents. For tumour cells adjacent to blood vessels in cords of SCC, the mean Mitotic Index was 2.1% and from this value a rapid potential doubling time could be inferred (approximately 31 to 66 h). The proportion of dead cells within cords of cervical SCC was higher than in animal tumours. Using measured values for cord radius and published equations that describe the diffusion and consumption of oxygen in metabolising tissue, an attempt was made to calculate the oxygen partial pressure in vessels of cords of these SCC.

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PubMed1985

Deriving absolute values of alpha and beta for dose fractionation, using dose-incidence data.

A method is described for calculating absolute "operational" values of the parameters alpha and beta that characterise dose fractionation data for tissues, by using the steepness of dose-incidence curves measured around each dose per fraction investigated. The values are deduced from published mouse lethality data after irradiation of the bone marrow (alpha = 0.9 Gy-1; beta = 0.06 Gy-2), the lung (alpha = 0.14 Gy-1; beta = 0.02 Gy-2), and the oesophagus (alpha = 0.06 Gy-1; beta = 0.004 Gy-2). With bone marrow and other hierarchical renewal tissues, the operational values apply also to the inactivation of target cells which are the stem cells in the tissue. For other tissue types the interpretation of the values is unknown. The operational values are useful in characterising the steepness of dose-incidence curves for normal tissue injury after different fractionation schedules.

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PubMed1984

Tumour-cord parameters in two rat hepatomas that differ in their radiobiological oxygenation status.

Tumour cords have been examined quantitatively in two rat hepatomas, 3924A and H-4-II-E, that differ in their radiobiological oxygenation status (oxygen enhancement ratio for growth delay [tumour clamped: tumor 'in air'] was 1.35 for 3924A and only 1.08 for H-4-II-E). The average thickness of tumour cords in 3924A was 118 microns and only 69 microns in H-4-II-E. The migration rates across the cords of the two tumours were approximately the same (1.7 and 1.4 micron X h-1) but for any given distance from the subtending blood vessel, the proportion of histologically-dead cells within the cord was always higher for H-4-II-E. Volume for volume, H-4-II-E contained four times as much vascular space as 3924A but it is suggested that the poor quality of this vasculature in H-4-II-E contributed to its relative radioresistance.

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PubMed1984

Death of intestinal crypts and of their constituent cells after treatment by chemotherapeutic drugs.

The number and spatial distribution of necrotic cells in the jejunal crypts of mice, has been measured after treatment by each of 6 cytotoxic drugs. At the LD10/8 day dose of each drug, the majority of necrotic cells were found below position 9 and numbers per crypt were similar for all drugs (approximately 8). These findings resemble those for radiation. However, major differences between agents were found in the calculated numbers of the microcolony-forming units (MFU) that determine overall crypt survival or ablation after high doses of cytotoxic agent. Numbers of MFU as assayed by radiation were approximately 80 per crypt, but only 2 when assayed by mechlorethamine hydrochloride, adriamycin and 5-fluorouracil, and 7 using BCNU. No crypts were destroyed by either cyclophosphamide or actinomycin D, despite the appearance of numerous necrotic cells in the lower part of the crypt. We conclude that in drug-treated intestine, necrotic cells may arise from a non-MFU compartment and the incidence and distributions of such cells are likely to be poor indicators of the response of the MFU.

Animals↗
PubMed1984

The proliferative status of microcolony-forming cells in mouse small intestine.

The technique of thymidine (TdR) suicide has been used with the intestinal microcolony assay to demonstrate that in the middle of the light cycle, nearly all intestinal clonogenic cells, in the B6D2F1 mice used in these experiments, were not in S phase. Doses of tritiated thymidine [3H]TdR up to 1 mCi/mouse did not kill a significant fraction of those clonogenic cells which survived a test dose of 12 Gy gamma-rays. This finding supports some data in the literature, but conflicts with others. However, the suicide technique was found in the studies reported here to be very efficient in sterilizing clonogenic cells in the middle of the dark cycle, and also in a regenerating epithelium at day 3 after a dose of 9 Gy. This implies that the technique can discriminate well between populations of clonogenic cells which differ in their content of cells in S phase. The lack of a suicide effect in the middle of the light cycle indicates that the majority of proliferative epithelial cells are not clonogenic.

Animals↗
PubMed1984

Differential effect of IP- and IV-injected nitrogen mustard on subsequently-irradiated intestinal crypts: implications for 'dose-effect factors' predicted by experimental, combined modality therapy.

In experimental chemotherapy-radiotherapy, cytotoxic drugs are almost invariably injected by the intraperitoneal (IP) route. This contrasts with normal clinical practice, which is to employ the intravenous (IV) route. We have used a clonogenic assay of gastrointestinal (GI) injury in mice to show that a given administered dose of nitrogen mustard (HN2), injected IP, results in a much greater reduction in the subsequent radiation dose required to achieve an isoeffect, than if the drug is injected IV. At an administered dose of 3.5 mg kg-1 of HN2 (the animal LD10/30 for IP injection), the radiation dose-reduction factor for 10% survival of intestinal crypts, was 1.94 for IP HN2 and only 1.28 for IV HN2. Even the grossly-equitoxic (mouse LD10/30) dose of IV HN2 resulted in a smaller predicted radiation dose reduction for GI injury, by a factor of 1.45. The validity of using the IP route in combined chemotherapy-radiotherapy studies designed to generate quantitative estimates of toxicity is discussed.

Animals↗
PubMed1983

Response of cell populations in tumor cords to a single dose of cyclophosphamide or radiation.

We have examined tumor cords of hepatoma 3924A in rats treated by 15 Gy of X-rays or 150 mg/kg of cyclophosphamide. Parameters measured were: cord thickness, cellular density, [3H]-TdR LI, MI and proportion of necrotic cells within the cord. With cyclophosphamide, a drop in cell density of 40% and in LI of 60% did not cause shrinkage of the cords. During the recovery phase, increase in cell number coincided with changes in the kinetics of the cell population adjacent to the capillary. For X-rays an approximately 10% decrease in cord thickness was associated with a rapid reduction in cell density and a relatively poor proliferative response of the cells adjacent to the vessel. There was little evidence for the sparing of remote cells with either agent. It did not appear that the progression of cells across the cord would be interrupted sufficiently for any 'spared' remote cells to participate in the therapeutic response.

Animals↗
PubMed1983

Dose-incidence curves for tumour control and normal tissue injury, in relation to the response of clonogenic cells.

A probit analysis has been made of data from the literature on local control of tumours and injury to normal tissue as a function of dose of radiation. Fifteen series were analysed for local tumour control in man and ten series for complications. The analysis yielded values for the D50 dose (50% incidence of effect) and the probit width (K), a measure of the steepness of the dose-incidence curve. The same analyses were made of data for rodents. Broadly, K was proportional to D50 in the ratio 1:7, with no major differences between tumours and reported complications. D50 was plotted as a function of dose per fraction for four normal tissues and two tumours in rodents. D50 decreased more rapidly with increasing dose per fraction for the normal tissues than for tumours. The probit width, K, varied inversely with increasing dose per fraction for normal tissues and this contrasted with the tumour response. Thus with increasing dose per fraction, the threshold for effect decreased and the steepness of the ensuing dose-incidence curve increased, relatively more rapidly for normal tissue than for tumour. These curves of gross response have been analysed also by the double negative log method of Gilbert [23], in an attempt to estimate the number and survival characteristics of "tissue-rescuing cells". These were calculated to be less than 1 in 10(4) of the numbers of clonogenic cells measured by excision assays. The D0 values of the derived survival curves for these tissue-rescuing cells were higher than those measured by excision assays.

Animals↗
PubMed1983

Topographic variations in the clonogenic response of intestinal crypts to cytotoxic treatments.

In the intestinal crypt microcolony assay, a "surviving fraction" of whole crypts is calculated conventionally by dividing the number of regenerating crypts three to four days after treatment by the number of crypts in untreated animals, both measured around a complete intestinal circumference in transverse sections of gut. We show that in relation to the mesenteric attachment of the gut, crypts in different regions of this circumference differ in their survival characteristics after radiation or mechlorethamine hydrochloride ("HN2"). Crypts associated with Peyer's patches are resistant to both agents (large initial shoulder, shallow slope). The mode of administration of HN2 (IP vs. IV) influences the shape of the crypt survival curve. Differences in size of shoulder and slope affect the estimate of numbers of microcolony-forming cells per crypt (A). For radiation, this number can vary sevenfold, depending on the region of circumference chosen for analysis. Different agents of assay result in radically different values for A.

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