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Biomedical subjects

H Johns

Publications and source records attributed to H Johns.

25 records · Page 2Linked to original sources
PubMed1991

Repopulation in murine skin after X-ray treatments with multiple fractions per day.

The kinetics of repopulation of clonogens in skin after fractionated X-ray exposures was studied in a series of experiments using a top-up design. The feet of mice were exposed to small X-ray doses (1.5 or 2 Gy), given two or three times a day on consecutive days with a minimum interfraction interval of 8 h. A single top-up dose of d(4)-Be neutrons was then given at various intervals after the last X-ray fraction, typically on Days 1,4,8, 15, and 19. The acute skin reaction produced was scored an analyzed by both a standard 23-day averaging and a 7-day averaging procedure. Either method gave similar results and led to the same conclusions. The amount of top-up dose needed to produce a fixed skin reaction was used as a measure of the net effect of the X-ray treatments. This net effect is a result of the initial reduction in skin clonogens due to X rays, and their repopulation before the top-up dose was given. Repopulation was not detected during any of these courses of fractionated treatment, up to an overall time of at least 12 and possibly 16 days. On completion of X-ray schedules lasting 6-16 days, repopulation started 4 days later. In contrast, this delay lengthened to approximately 8 days for shorter overall treatment times of 3-4 days. Once repopulation started, it proceeded rapidly over 11 days so that by 15 days after the cessation of X rays, the skin was restored almost to its normal state with respect to radiosensitivity. The residual damage from Day 15 to Day 19 postirradiation was 3-13% of a full-effect level. The rate of repopulation can be expressed as a clonogen doubling time (Tclon), assuming that an average skin reaction of 1.5 is equivalent to a clonogen surviving fraction of 1.7 x 10(-5). Tclon varied inversely with the amount of initial damage inflicted by the X rays, with the shortest values (1-1.3 days) seen following X-ray doses that gave an initial damage level of 60-80% of full effect. These data are consistent with a hypothesis that damage is "sensed" only 10-12 days after the first X-ray fraction, which provides the stimulus for repopulation of the target cells in the basal layer, the keratinoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Recovery kinetics in mouse skin and CaNT tumours.

Recovery kinetics and recovery capacity were studied in a fast proliferating normal tissue, skin, and in an anaplastic mouse mammary carcinoma, CaNT. Three fractions per day of X-rays, repeated over 5 days, were given at varying interfraction intervals from 0 to 8 h. The rate of recovery in tumours (t1/2 = 0.31 +/- 0.15 h for local control) was significantly faster than in skin (t1/2 = 0.96 +/- 0.10 h). By contrast, the fractionation sensitivity of CaNT tumours was less than that of skin (alpha/beta = 43.3 +/- 8.5 Gy vs. alpha/beta = 7.9 +/- 0.2 Gy). Tissues with recovery half-times similar to or longer than that determined for skin would be at risk if interfraction intervals less than 6 h are used in regimes which involve the use of two or more fractions per day. This would be especially true for tissues that show a greater sensitivity to dose fractionation, and hence more sparing of radiation damage with hyperfractionation.

Adenocarcinoma↗
PubMed1989

Role of glutathione peroxidase in the radiation response of mouse kidney.

Glutathione peroxidase (GSH-Px) has been implicated in mediating the radioprotective effects of glutathione (GSH). This hypothesis was tested in vivo by determining the effect of GSH-Px depletion on the radiation response of murine kidneys. Renal GSH-Px levels were depleted to 17% of control values by feeding animals a selenium deficient diet for 6 weeks; this had no significant effect on renal levels of GSH or GSH-S-transferase (GST). However, we also tested the effect of direct depletion of GSH to 3-4% of control values, using a combination of DL-buthionine sulphoximine (BSO) and diethyl maleate (DEM). Kidneys with normal or depleted levels of GSH-Px and/or GSH were irradiated with 240kVp X rays (2 fractions, 7 days apart to minimize intestinal injury). Mice breathed 7% oxygen during irradiation. Renal damage was assessed at 20, 25, and 32 weeks after the first fraction of X rays, in terms of reduced hematocrit and renal clearance of 51Cr-EDTA. Depletion of GSH-Px levels to 17% of control did not alter renal radiosensitivity, but depletion of GSH to 3-4% of control values radiosensitized the kidney by a factor of 1.4. Depletion of both GSH and GSH-Px together did not radiosensitize the kidney any more than was achieved by GSH depletion alone.

Animals↗
PubMed1989

Does the repair capacity of skin change with repeated exposure to X-rays?

A sensitive experimental design and data analysis were used to test rigorously whether the repair capacity in the skin of the mouse foot changes during a course of repeated 240 kVp X-ray doses. Any such changes might reflect saturation or induction of repair enzymes resulting from progressive radiation damage, but most importantly this assumption of equal effect per dose fraction is central to all analyses of multiple-fraction radiation treatments, and remained to be demonstrated conclusively in skin. An X-ray dose of 2.5 Gy was given two, eight, 14 or 20 times with an interfraction interval of 8 h. Individual skin reactions for each mouse were analysed separately, giving 139 estimates of the effectiveness of 2.5 Gy (approximately 35 in each of the four fractionation schedules). Regression analysis of effect per fraction versus number of fractions showed that there was no significant trend, i.e. the damage per fraction was constant regardless of the number of fractions used. The mean damage per fraction was 3.75 +/- 0.15 per cent (95 per cent CL) of the full underlying damage equivalent to transient moist desquamation, and the slope of this plot was 0.0075 per cent +/- 0.022 per cent (95 per cent CL) per fraction. It was concluded that the assumption of equal effect per fraction was not invalidated in mouse skin. Shorter interfraction intervals would not allow full repair between fractions, and this could be misinterpreted as a progressive loss of repair capacity in this type of experiment. This was tested in skin by giving 2.5 Gy doses two, eight and 14 times with a 1-h interfraction interval. Effect per fraction increased with number of fractions, by an extra 37 per cent from two to eight fractions and by a further 14 per cent from eight to 14 fractions, giving the illusion of loss of repair as predicted. This confirms the need to check that where loss of repair capacity is suspected, this is not due artifactually to incomplete repair between fractions in slowly repairing systems.

Animals↗
PubMed1988

Renal damage in the mouse: the response to very small doses per fraction.

Experiments were undertaken to study the effect on the mouse kidney of repeated X-ray doses in the range 0.2 to 1.6 Gy per fraction and neutron doses in the range 0.05 to 0.25 Gy per fraction. A top-up design of experiment was used, so that additional graded doses of d(4)-Be neutrons (EN = 2.3 MeV) were given to bring the subthreshold damage produced by these treatments into the measurable range. This approach avoided the necessity to use a large number of fractions to study low doses per fraction. Renal damage was assessed using three methods: 51Cr-EDTA clearance, urine output, and hematocrit at 16-50 weeks postirradiation. The dose-response curves obtained were resolved best at 29 weeks. However, the results were also examined by fitting second-order polynomials to the data for response versus time postirradiation and using interpolated values from these functions at 29 weeks to construct dose-response curves. This method reduced slightly the variation in the dose-response data, but the interrelationship between the dose-response curves remained the same. The data were used to test the linear-quadratic (LQ) description of the underlying X-ray dose-fractionation relationship. The model fits well down to X-ray doses per fraction of approximately 1 Gy, but lower X-ray doses were more effective per gray than predicted by LQ, as seen previously in skin [M. C. Joiner et al., Int. J. Radiat. Biol. 49, 565-580 (1986)]. This increased X-ray effectiveness and deviation from LQ are reflected directly in a decrease in the RBE of d(4)-Be neutrons relative to X-rays at low doses, since the underlying response to these neutrons is linear in this low-dose region. The RBE decreases from 9.9 to 4.7 as the X-ray dose per fraction is reduced below 0.8 Gy to 0.2 Gy, reflecting an increase in X-ray effectiveness by a factor of 2.1. A model is discussed which attempts to explain this behavior at low doses per fraction.

Animals↗
PubMed1987

Renal damage in the mouse: the effect of d(4)-Be neutrons.

A further study on the response of the mouse kidney to d(4)-Be neutrons (EN = 2.3 MeV) is described. The results confirm and augment the work published previously by Stewart et al. [Br. J. Radiol. 57, 1009-1021 (1984)]; the present paper includes the data from a "top-up" design of experiment which extends the measurements of neutron RBE (relative to 240 kVp X rays) down to X-ray doses of 0.75 Gy per fraction. The mean RBE for these neutrons increases from 5.8 to 7.3 as X-ray dose per fraction decreases from 3.0 to 1.5 Gy in the kidney. This agrees with the predictions from the linear quadratic (LQ) model, based on the renal response to X-ray doses above 4 Gy per fraction. The mean RBE estimate from a single dose group at 0.75 Gy per fraction of X rays is, however, 3.9. This is below the LQ prediction and may indicate increasing X-ray sensitivity at low doses. Data from this study and from those published previously have been used to determine more accurately the shape of the underlying response to d(4)-Be neutrons; an alpha/beta ratio of 20.5 +/- 3.7 Gy was found. The best value of alpha/beta for X rays determined from these experiments was 3.04 +/- 0.35 Gy, in agreement with previous values.

Animals↗