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Biomedical subjects

R W Hart

Publications and source records attributed to R W Hart.

At least 145 records · Page 8Linked to original sources

Comparative metabolism and DNA binding of 7,12-dimethylbenz[a]anthracene and its weakly carcinogenic 5-fluoro analog.

Cultured Syrian hamster embryo cells readily convert both the carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA), and its weakly carcinogenic analogue, 5-fluoro-7,12-dimethylbenz[a]anthracene (5F-DMBA), to water soluble metabolites. DMBA, however, binds to the hamster cell DNA at least 2.8-3.0 times more extensively than 5F-DMBA. Likewise, 5F-DMBA is converted to water soluble metabolites by liver microsomal preparations at a rate equal to DMBA, but the latter compound binds to DNA 2.6-3.2 times more effectively.

9,10-Dimethyl-1,2-benzanthracene↗

Changes in growth and morphology of human gliomas and fibroblasts cultured in D-valine medium.

Human fibroblasts and cells cultured from a glioblastoma multiforme and and oligodendroglioma were grown in standard tissue culture medium and in a medium in which D-valine was substituted for L-valine (DVM). Growth of all three types of cells was inhibited in DVM. Morphological changes of cells cultured in DVM also occurred: many fibroblasts became stellate-shaped and the oligodendroglioma cells had fewer processes. These findings indicate that DVM can not be used to decrease fibroblastic contamination in cultures of human gliomas without altering the morphological and growth characteristics of the neoplastic cells.

Brain Neoplasms↗

Lipid composition of human neural tumors.

Gangliosides, cholesterol, and phospholipids were quantitated in the tissues of 11 human neural tumors and the cells of two gliomas cultured in vitro. All tumor tissues contained higher water concentrations but lower total lipid concentrations than either human grey or white matter. In general they contained less cholesterol, sphingomyelin, and serine glycerophospholipid but more choline glycerophospholipid than white matter. Concentrations of total ganglioside sialic acid were intermediate between grey and white matter. Compared with normal brain, all tumors had greater proportions of the structurally less complex gangliosides and smaller proportions of the more complex gangliosides. This was most marked in the rapidly growing tumors while the better differentiated astrocytomas contained the greatest proportions of complex gangliosides. The cells of the cultured tumors contained amounts of total lipid and total phospholipid similar to their parent tissues. However, the cultures had less cholesterol, sphingomyelin, and total ganglioside than their parent tissues. There were significant amounts of choline and ethanolamine plasmalogens in both cultures and parent tissues. The ganglioside patterns of both cultures were complex but they contained a greater proportion of structurally simpler gangliosides than their parent tissues.-Yates, A. J., D. K. Thompson, C. P. Boesel, C. Albrightson, and R. W. Hart. Lipid composition of human neural tumors.

Astrocytoma↗

Pesticide induced ouabain resistant mutants in Chinese hamster V79 cells.

The effect of 3 insecticides (chlordane, dieldrin and carbaryl) and one herbicide (2,4-D-fluid) was studied on the induction of ouabain-resistant mutants in Chinese hamster V79 cells at concentrations approaching the Environmental Protection Agency (EPA) tolerance limits. The kinetics and dose range for cytotoxicity were determined by colony formation assay. Results showed that these compounds enhanced the number of ouabain-resistant mutants and acted as weak mutagens.

2,4-Dichlorophenoxyacetic Acid↗

Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells.

Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive "error-free" postreplication repair process, allows an "error-prone" DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties.

Caffeine↗

Pesticide induced DNA damage and its repair in cultured human cells.

The effects of pesticides on the induction of unscheduled DNA synthesis in SV-40 transformed human cells (VA-4) in culture with and without metabolic activation by liver microsomes was studied. Results showed that ten of the thirteen compounds examined either directly or upon metabolic activation induced unscheduled DNA synthesis in the human cell system used. The DNA repair kinetics and size of the repaired regions resulting from treatment with four of the chemicals (Carbaryl, Chlordane, Dieldrin and 2.4-D Fluid) were studied by 313 nm photolysis of repaired regions containing bromodeoxyuridine (BUdR). The size of the repaired regions differed between compounds but could generally be classified as either of the X-ray (short) or UV-type (long).

Cell Line↗

Study of trans-cyclopropylbis (diketopiperazine) and chelating agents related to ICRF 159. Cytotoxicity, mutagenicity, and effects on scheduled and unscheduled DNA synthesis.

The cytotoxicity, mutagenicity, and DNA damaging potential of trans-cyclopropylbis (diketopiperazine) (3) and chelating agents related to ICRF 159 (1) were examined as a function of concentration and duration of exposure in the Chinese hamster cell line V79A. At a concentration of 10(-3) M, 1 and the trans-cyclopropanediamine tetraacid 8 and ester 7 proved to be cytotoxic and mutagenic. The trans-cyclopropyl analogue 3 of ICRF 159 and acyclic tetraacid 6 were less cytotoxic at all concentrations; analogue 3 exhibited no mutagenic activity at any of the concentrations tested. Compounds 1, 7, and 8, at lethal concentrations, exhibited significantly different mutation frequencies with 7 being sixfold more mutagenic than 8 at the same molar concentration. At 10(-3) M compounds 8 was several times more effective blocking DNA replication than other analogues but did not induce unscheduled DNA synthesis as did 1,3, and 6. With the exception of 8, there was an excellent correlation between mutagenesis and the induction of unscheduled DNA synthesis.

Animals↗

Evidence that pyrimidine dimers in DNA can give rise to tumors.

The Amazon molly, Poecilia formosa, is a small fish that grows in clones. Hence, cells from one animal may be transplanted to another without danger of rejection. Cells from thyroid and adjacent tissue were irradiated with UV light in vitro and injected into the abdominal cavity of isogeneic recipients. At appropriate UV doses and numbers of cells injected, all recipients showed exuberant thyroid proliferation. We give arguments and data indicating that the proliferation is a tumor, not a goitrogenic response. If the UV irradiation is followed, but not preceded, by photoreactivating illumination, the yield of thyroid growths is markedly decreased. Because other investigations have shown that photoreactivation monomerizes UV-induced cyclobutylpyrimidine dimers in DNA and does not affect other photoproducts, our data indicate that pyrimidine dimers in DNA can give rise to tumors.

Animals↗

A comparison of survival and repair of UV-induced DNA damage in cultured insect versus mammalian cells.

Survival and unscheduled DNA synthesis (UDS) were measured in a cultured insect cell line, TN-368, and a cultured mammalian cell line, V-79-4, following exposure to several fluences of ultraviolet light. TN-368 cells were approximately seven times more resistant to the lethal effects of UV than V-79 cells, as determined by colony formation. The amount of UDS per unit amount of DNA is about the same in both cell types 4 hr after 10-50 J/m2 UV irradiations.

Animals↗

Tissue changes resulting from the injection of gamma-irradiated cells into the gynogenetic teleost, Poecilia formosa.

In previous studies a clone of the gynogenetic fish, Poecilia formosa (the Amazon molly), was successfully used as a test animal to identify ultraviolet-induced damage. This work has been extended, and the fish system was used to detect damage caused byionizing radiation. Fish cells, exposed in vitro to 250 and 500 rads, were injected into young isogenic recipients, and 9 months later the fish were examined grossly and histologically. Two of the most conspicuous changes that resulted were the development of extensive invasive thyroid hyperplasia and hypertrophy body, with an apparent reduction in the amount of hemato-poietic tissue in the head kidney and spleen. We discuss the difference between the responses of the recipient fish to cells exposed to ionizing radiation and to cells exposed to ultraviolet light.

Animals↗