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D Kram

Publications and source records attributed to D Kram.

11 recordsLinked to original sources
PubMed1979

Cytokinetic analysis of the impaired proliferative response of peripheral lymphocytes from aged humans to phytohemagglutinin.

The effect of donor age on the rate of cell entry into the proliferating pool and subsequent cell cycle duration for peripheral lymphocytes stimulated by phytohemagglutinin (PHA) were examined by using the bromodeoxyuridine incorporation-differential staining technique. Distribution curves for the appearance of metaphase cells in successive generations as a function of culture time were obtained and analyzed both graphically and by a computer simulation model. Peripheral lymphocytes from aged individuals (approximately 75 yr) were stimulated by PHA at approximately one-half of the rate of peripheral lymphocytes from young individuals (approximately 21 yr). Subsequent cell-cycle durations were estimated to range from 10.0 to 25.0 h for aged individual lymphocyte cultures and 10.6-15.6 h for young individual lymphocyte cultures. The possible significance of these findings to aging in general is discussed.

Adult↗
PubMed1979

Spontaneous and mitomycin-C induced sister-chromatid exchanges. Comparison of in vivo and in vitro systems.

Frequencies of sister-chromatid exchanges (SCE) were measured in vitro in mouse fibroblasts and in vivo in mouse bone-marrow cells. SCE levels in these cell systems were measured in response to varying concentrations of bromode-oxyuridine (BrdU) and mitomycin-C (MMC). Although BrdU was found to induce SCE in both cellular systems, baseline SCE levels were 2- to 3-fold higher in vitro than in vivo. SCE induction was found to be a linear function of MMC concentration in vivo and in vitro; however the slope of the vivo curve was 5-fold higher. The interaction of BrdU substituted DNA and MMC was examined by administering a fixed dose of MMC with increasing concentrations of BrdU. The induced SCE frequencies appeared to be additive. In addition to measuring drug-induced SCE, the BrdU differential staining technique allows concomitant measurement of the inhibition of cellular replication by the test drugs.

Animals↗
PubMed1979

The effect of aging on sister chromatid exchange.

The advent of the bromodeoxyuridine(BrdU)-differential staining techniques has greatly facilitated the detection of sister chromatid exchanges (SCE). These SCE have been demonstrated to be an accurate reflection of DNA damage both in vitro in cultured cells and in vivo in mouse and rate bone marrow and spleen cells. In this review, we examine the effect of cellular aging on both baseline and mutagen-induced SCE levels. In all systems examined, aging did not appear to significantly affect the baseline levels of SCE. However, in human fibroblast cultures we have found a significant decrease in the levels of mutagen-induced SCE as a function of both in vitro passage level (in vitro aging) and the age of the cell culture donor (in vivo aging). In addition we have found a similar decrease in mutagen-induced SCE levels in both mouse and rat bone marrow cells and mouse spleen cells where examinations were performed entirely in vivo. Diminished mutagen-induced SCE levels were obtained with a wide variety of agents including mitomycin-C, cyclophosphamide, adriamycin, ethyl methanesulfonate and N-acetyl-2-acetoxyamino-fluorene. These decreased SCE levels were accompanied by increased frequencies of chromosomal aberrations in the older cell populations. If SCE represents a form of DNA repair as has been suggested by several investigators, our finding would indicate impaired DNA repair occurring in old cells.

Aging↗
PubMed1979

Cellular replication and aging.

Controversy exists concerning the effect of aging on replicating cell systems. This review summarizes a number of studies which indicate that both in vivo and in vitro, cell replication is significantly altered during aging. In vitro, studies of both human lymphocytes and fibroblasts indicated that a number of replication kinetic parameters are influenced by the age of the cell donor. In vivo, the application of the bromodeoxyuridine-(BrdU)-differential chromatid staining techniques to the analysis of cellular replication kinetics has permitted us to demonstrate that cellular replication is also significantly diminished with aging in mouse and rat cell populations. Therefore, both in vivo and in vitro in human as well as rodent cell populations, the rates of cellular replication are significantly decreased with cellular aging.

Aging↗
PubMed1979

Aging and sister chromatid exchange. IV. Reduced frequencies of mutagen-induced sister chromatid exchanges in vivo in mouse bone marrow cells with aging.

Induction of sister chromatid exchanges (SCE's) was examined in bone marrow cells of young and old C57BL/6J mice exposed to three different DNA-damaging agents (cyclophosphamide, mitomycin C, and doxorubicin). At low concentrations of all three mutagens, the levels of induced SCE's were similar in young and old cell populations. However, at higher mutagen concentrations, SCE induction was significantly reduced in old cell populations. Studies of mice aged 5 to 32 months revealed that induced SCE frequencies remain stable during early adulthood (5 to 12 months) and then begin to decline as a function of age. These results indicate that with aging there exists a gradual alteration of cellular response to DNA damage.

Animals↗
PubMed1978

Reduced frequencies of mitomycin-C induced sister chromatid exchanges in AKR mice.

The frequencies of base-line and Mitomycin-C (MMC) induced sister chromatid exchanges (SCE) were surveyed in four inbred strains of mice. In contrast to the C57Bl/6J, CBA/J, and A/J strains where frequencies of SCE increased linearly with increasing dose of MMC, levels of SCE were significantly lower in AKR/J mice at high MMC concentrations. At a dose of 5 mg/kg MMC, chromosomal aberrations were more frequent in bone marrow cells of AKR/J mice than in C57Bl/6J mice. These observations suggest an altered response to DNA damage in the AKR mouse strain.

Animals↗
PubMed1978

The effects of high and low fluoride diets on the frequencies of sister chromatid exchanges.

A recent report suggests that fluoride has mutagenic activity in mice. To examine the potential clastogenic effect of ingested fluoride, we examined the frequencies of baseline SCE and mitomycin C induced SCE as well as baseline chromsomal aberrations and cell-cycle kinetics in mice raised on high and low fluoride diets. The lack of significant differences in any of these parameters between the two groups of animals indicates that dietary fluoride is not clastogenic and supports the continued use of water fluoridation.

Animals↗