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Biomedical subjects

R W Hart

Publications and source records attributed to R W Hart.

At least 163 records · Page 9Linked to original sources

Direct evidence that pyrimidine dimers in DNA result in neoplastic transformation.

A specific test for the biological role of UV-induced pyrimidine dimers in DNA is photoreactivation (PR). Fish contain large amounts of the PR enzyme. Portions of cell suspensions of tissue from various organs of the fish Poecilia formosa were exposed to UV radiation (254 nm), then injected into isogenic recipients. An incident fluence of 20 J/m2 resulted in 10% of the fish with large granulomas and 100% with thyroid carcinomas. If the irradiated cell suspension was illuminated with PR light before injection, the yields of both types of lesion were reduced approximately 10-Fold. If the PR light was given before the UV exposure, there was no reduction in the numbers of growths. These experiments show that pyrimidine dimers in DNA can lead to neoplastic transformation.

Animals↗

DNA repair and life span of mammals.

The ability of fibroblasts to perform unscheduled synthesis (a measure of excision-repair) after UV irradiation was measured autoradiographically for seven mammalian species at several times after UV irradiation. The initial rate and the maximum incorporation of [3H]dThd increased with the life span of the species.

Animals↗

A radioprotective stereostructure-activity study of cis- and trans-2-mercaptocyclobutylamine analogs and homologs of 2-mercaptoethylamine.

For purposes of studying stereostructure-activity relationships at the molecular, cellular, and animal levels and probing the mechanism of 2-mercaptoethylamine (MEA) radioprotection we synthesized several conformationally constrained cyclobutyl analogs. The comparative radioprotective properties for MEA, cis- and trans-2-mercaptocyclobutylamine (2), cis- and trans-2-mercaptocyclobutylmethylamine (3), and trans-2-mercaptomethylcyclobutylamine (4) are discussed in terms of their ability to chemically reduce transient free radicals, the formation of single strand breaks in DNA, and protect Chinese hamster cells (in vitro) and mice against the lethal effects of ionizing radiation. The results are interpreted in light of current proposed mechanisms of action for MEA. No correlation exists between ability of these analogs to enhance mice survival times and their ability to protect against the induction of DNA single strand breaks and the inactivation of proliferative capacity of hamster cells growing in vitro. Analysis of two isomers (cis- and trans-3) on the repair of single strand breaks showed both isomers only marginally influenced the rate and did not influence of extent of single strand break rejoining. The results are consistent with a mode of action involving chemical repair of transient radicals and protection against DNA and critical enzymatic sites.

Animals↗

Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species.

The ability of fibroblasts to perform unscheduled DNA synthesis (a measure of excision-repair) after UV irradiation was measured radioautographically for seven species at several times after several UV fluences. Both the initial rate and the maximum incorporation of [(3)H]dThd increased with the life-span of the species (shrew, mouse, rat, hamster, cow, elephant, man). Unscheduled DNA synthesis was approximately proportional to the logarithm of life-span.

Aging↗

The transparency of the mammalian cornea.

1. A theoretical and experimental analysis of the relationship of the corneal stromal ultrastructure with light transmission has been made in an attempt to resolve recent contradictory explanations of corneal transparency.2. The spatial distribution of collagen fibrils in electronmicrographs of rabbit corneal stroma has been analysed in terms of a radial distribution function. The results indicate the presence of local order extending to at least 200 nm from individual fibrils.3. The observed spatial distribution of the collagen fibrils was used as a basis to compare the theoretically derived and the experimentally determined values of light transmission. It has been found that the transparency of the normal cornea may be explained by the quasi-random structure revealed by the electronmicroscope.4. Histograms of the collagen fibril diameter in normal rabbit corneal stroma revealed the range to be 12.5-32.5 nm and the mean value to be approximately 20 +/- 1.5 nm. Corneal swelling did not change the collagen fibril diameter significantly.5. It is concluded that the size and distribution of collagen fibrils revealed in electronmicrographs are consistent with the observed transparency of normal stromas.6. A marked heterogeneity in the spatial distribution of collagen fibrils was found in the swollen cornea. This is qualitatively consistent with the observed decrease in transparency.

Animals↗