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D H Blakey

Publications and source records attributed to D H Blakey.

26 records · Page 2Linked to original sources

Comparison of the effects of 1,2-dimethylhydrazine and cyclophosphamide on micronucleus incidence in bone marrow and colon.

An in vivo micronucleus assay has been developed that utilizes colonic epithelial cells. The genotoxic effects of 1,2-dimethylhydrazine (54-07-3), a colon carcinogen, and of the nitrogen mustard, cyclophosphamide (50-18-0), on the bone-marrow polychromatic erythrocytes and on colonic epithelium from mice were compared using micronucleus induction in each organ as the end point. In the bone marrow, cyclophosphamide was a potent inducer of micronuclei, while 1,2-dimethylhydrazine administration had little effect on the micronucleus incidence. In the colon, 1,2-diemthylhydrazine was an effective inducer of micronuclei. Thus, the colonic micronucleus assay appears to be a potentially useful test for the detection of colon carcinogens.

1,2-Dimethylhydrazine↗

The effect of stannous and stannic (tin) chloride on DNA in Chinese hamster ovary cells.

Tin(II) at concentrations up to 500 microM stannous chloride (SnCl2), produced extensive DNA damage, as detected by alkaline sucrose gradient (ASG) analysis in Chinese hamster ovary (CHO) cells treated for 1 h at 37 degrees C in serum-free minimal essential medium (MEM). However treatment of cells with tin(IV), as stannic chloride (SnCl4), produced no such DNA damage. There was no loss in colony formation 6 days after either treatment suggesting that the DNA damage induced by the tin(II) was rapidly repaired and/or that DNA synthesis proceeded on the damaged templates permitting cell division to occur. Alternatively, the type of DNA damage caused by tin(II) may not lead to a reduction in colony-forming ability. Tin(II) produced about 200 times more ASG detectable DNA damage on an equi-molar basis than did Cr(VI), a known human carcinogen. This study indicates that tin(II) may be potentially genotoxic.

Animals↗

Diurnal variation in the response of gamma-ray-induced apoptosis in the mouse intestinal epithelium.

The appearance of apoptosis has been used as an index of carcinogen-induced damage incurred by the intestinal epithelium. Here we report that the cytotoxic response elicited by gamma radiation in the duodenal and colonic epithelium of the mouse is markedly affected by the time of day at which the animals are irradiated or sampled. The diurnal pattern in radiosensitivity of the crypt cells, as measured by the appearance of apoptosis is reflective of circadian rhythms in mouse intestinal cells. Circadian effects should therefore be considered when interpreting apoptosis data obtained at one time point only or when comparing data obtained at different times of the day.

Animals↗

Transient DNA lesions induced by benzo[a]pyrene in Chinese hamster ovary cells.

Alkaline sucrose gradient sedimentation analysis was used to detect DNA lesions induced by benzo[a]pyrene B(a)P in Chinese hamster ovary cells. The number of lesions detected immediately following treatment with 10(-4) M B(a)P was related directly to the duration of treatment. When treated cells were incubated in a B(a)P-free medium, the majority of lesions disappeared rapidly and could no longer be detected 15 min following treatment. These data indicate that a population of B(a)P-induced DNA lesions may be removed by a rapid DNA-repair process. The transient nature of such lesions should be considered when assays for DNA damage or repair are designed and interpreted.

Animals↗

Mutagenic activity of p-toluenesulfonhydrazide.

Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there is relatively little toxicological data. In this study, the mutagenic activity of TSH was determined in the Salmonella/mammalian microsome assay and the in vitro chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene mutations both with and without metabolic activation in the Salmonella/mammalian microsome assay but that it did not induce chromosomal aberrations in Chinese hamster ovary cells. The results of this study indicate that TSH is an in vitro mutagen and should be assessed for in vivo mutagenicity.

Animals↗