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Biomedical subjects

A G Searle

Publications and source records attributed to A G Searle.

13 recordsLinked to original sources
PubMed1979

A disruption of pachytene DNA metabolism in male mice with chromosomally-derived sterility.

DNA metabolism was analyzed in spermatocytes of mice that were sterile either because of X-autosome or autosome-autosome translocations, or because of trisomy. In the strains analyzed, spermatogenic development is arrested by metaphase I or soon thereafter. In all such strains a disruption of the normal pattern of pachytene DNA metabolism occurred. Prepachytene metabolism appeared normal. Disruption was manifest in both the level of endogenously generated nicks during pachytene and in the distribution of nicks among the different DNA sequence classes. Nicking was more intense in the steriles and tended to be randomized in distribution. Satellite DNA underwent pachytene nick-repair in the steriles but not in fertile controls. The repair capacity of spermatocytes from steriles was equal to that of the fertiles; the higher frequency of nicks in the steriles was due to a persistence of nicking activity.

Animals↗
PubMed1979

Hereditary damage.

For the purposes of radiation protection, risk estimates should be based on effects of irradiation at low doses and low dose-rates. Although few genetic studies have been made on effects at low doses those carried out at low dose-rates suggest that the response is generally linear for induction of both gene mutations and chromosomes aberrations. For obtaining an overall genetic risk assessment under these conditions a doubling dose of 100 rem (1 Sv) has been used by the ICRP and other bodies, with respect to radiation of low LET. In addition, it is necessary to know frequencies of human hereditary conditions, the extent to which these frequencies are maintained by recurrent mutation and the average number of generations the different categories of hereditary damage persist in the population. By the use of this information, as well as some data on translocation induction obtained directly from human exposures, an estimate of the risk of serious hereditary ill health in the first two generations after low-level radiation exposure was obtained for the Commission by one of its task groups. Thus the estimate of 10-2 Sv-1 used in ICRP 26 has a factual basis, although a number of far-reaching assumptions have still to be made when any risk estimation of this nature is attempted.

Animals↗
PubMed1979

Colinearity in the mouse genome: a study of chromosome 2.

The cytologic positions (determined by G-banding) of the breakpoints on mouse chromosome 2 of a series of ten reciprocal translocations were compared with their most probable genetic positions on the linkage map, as determined by studies on recombination with known chromosome 2 (= linkage group V) markers. The most probable proximaldistal orders of the genetic and cytologic breakpoints were found to be the same; i.e., the two sets of breakpoints were colinear. However, there was no close correspondence between these two measures of the distance apart of adjacent breakpoints, since some translocation breaks which were well separated in G-band positions seemed close together in terms of the linkage map, and vice versa. This helps to confirm LYON'S conclusion that in certain mouse chromosomes, including No. 2, the distribution of chiasmata is nonrandom.

Animals↗
PubMed1977

The use of pigment loci for detecting reverse mutations in somatic cells of mice.

The retinal pigment epithelium (RPE) consists of a single layer of hexagonal cells, numbering about 10(5) in the 3-day mouse. Examination of the fixed and cleared RPE of mice homozygous for the unstable allele of pink-eye (pun), which shows a relatively high frequency of reversion to wild type, has revealed that the pigmented cells which result from such reversions (mainly arranged singly or in small clonal groups) can be detected with relative ease on the unpigmented RPE background. It is felt, therefore, that this system should provide a suitable way of studying somatic reversions induced by chemical agents in pink-eyed mutations of the mouse and other mammals.

Animals↗
PubMed1976

Cytogenetic effects of protracted exposures to alpha-particles from plutonium-239 and to gamma-rays from cobalt-60 compared in male mice.

Adult C3H X 101 hybrid male mice were injected intravenously with 4 muCi of 239Pu citrate per kg body weight and examined for evidence of cytogenetic damage to the testis after exposures of 21, 28 and 34 weeks, with average doses from alpha-particles estimated as 13, 18 and 18 rad respectively (mean dose rate 0.00006 rad/min). Results were compared with those obtained when equivalent males were exposed continuously and concurrently to 1128 rad 60Co gamma-irradiation over 28 weeks (0.004 rad/min). The following estimates of the relative effectiveness of the alpha- and gamma-radiation were made: 24 for reciprocal translocations and for chromosome fragments, 22 for dominant lethal mutations acting after implantation. These values (with mean of 23) are based on average testis doses, with no correction for probable non-homogeneity of alpha dose distribution. In the mice exposed to gamma-irradiation there were significant reductions in testis mass and epididymal sperm-count. Although corresponding differences from control were not significant in the alpha series, consideration of results from a previous experiment by the same authors [2] allowed the relative effectiveness of the alpha- and gamma-irradiation for testis mass reduction to be estimated as roughly 10-15. Existing data on translocation induction in mouse spermatogonia by low dose-rates of gamma-rays (down to 0.003 rad/min) were analysed. They suggested that minimum rates of induction at very low intensities were not less than 1 X 10(-5) translocations per rad. A comparison of the frequencies of induction of fragments and of sperm-head abnormalities obtained after chronic gamma-ray exposures in the present experiment with those found by other workers after acute X-ray exposures suggested that there were no marked dose-rate effects with these types of mutational effect. Finally, the special problems associated with cytogenetic studies on alpha-emitters are discussed.

Alpha Particles↗