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M K Conner

Publications and source records attributed to M K Conner.

30 records · Page 2Linked to original sources
PubMed1982

Comparison of sister chromatid exchange induction and known carcinogenic activities of vinyl and allyl carbamates.

In vivo sister chromatid exchange (SCE) induction by vinyl and allyl carbamates was examined in alveolar macrophage, bone marrow, and regenerating liver cells of C57BL/6J x DBA/2J F1 mice. Allyl carbamate was effective in producing increases in SCE frequencies (relative to base-line SCE) over a dose range of 220 mumol/kg (approximately 2 times base line) to 2.2 mmol/kg (3 times base line). In general, alveolar macrophage and regenerating liver cells had higher responses, although not significantly, than did bone marrow. Vinyl carbamate produced significant increases in SCE frequencies over a dose range of 10 mumol/kg (2 times base line) to 75 mumol/kg (8 to 10 times base line). At the highest dose, SCE frequencies in extrahepatic tissues of hepatectomized mice were significantly higher than in intact mice and, within hepatectomized mice, alveolar macrophage and regenerating liver cell responses were greater than were bone marrow responses. Vinyl carbamate was approximately 30 times as potent a SCE inducer than we reported previously for ethyl carbamate. To date, our studies of six different carbamate esters have indicated a striking similarity in relative potencies for SCE induction and their known tumorigenic potencies.U

Animals↗
PubMed1982

In vivo sister chromatid exchange and cellular replication kinetics of normal and lymphoma AKR bone marrow cells.

The recent development of an AKR(Rb6.15)1Ald lymphoma model in our laboratory presents a unique means of comparing sister chromatid exchange (SCE) frequencies and cellular replication kinetics of normal and lymphoma cells in the same host environment. Lymphoma cells, distinguished from normal cells by the presence of two metacentric chromosomes, had an average cell cycle time of 8 hr compared to 11 hr for normal cells. Normal bone marrow cells from nonleukemic AKR/J, nonleukemic AKR(Rb6.15) Ald, and tumor passage recipients had similar baseline and 1,3-bis(2-chloroethyl)-1-nitrosourea-induced SCE frequencies following exposure to 4.4 mg 1,3-bis(2-chloroethyl)-1-nitrosourea per kg and 19 hr 5-bromo-2-deoxyuridine. While baseline SCE frequencies were only slightly higher, 1,3-bis(2-chloroethyl)-1-introsourea-induced lymphoma cell SCE frequencies were 3 times higher than normal induced SCE frequencies [34.06 +/- 6.6 (S.E.) versus 11.0 +/- 0.6 SCEs/cell].

Animals↗
PubMed1982

Cellular replication kinetics and persistence of sister chromatid exchange-inducing lesions in normal and lymphoma AKR cells following exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea.

The present studies were designed to evaluate the role of cell cycle time and time of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) administration on the persistence of sister chromatid exchange (SCE)-inducing lesions in normal and lymphoma second- and third-division AKR bone marrow cells. Normal second-division cells harvested from mice given injections of BCNU at the start of an 18-, 24-, or 28-hr 5-bromo-2-deoxyuridine (BrdUrd) infusion exhibited similar linear dose-dependent increases in SCE frequencies (p greater than 0.05). The faster-cycling lymphoma cells, harvested after 18-hr BrdUrd infusion, had significantly higher baseline (p less than 0.05) and BCNU-induced increases (p less than 0.001) in SCE frequencies than did normal cells. Dose-dependent increases in SCE frequencies were demonstrated in third-division normal and lymphoma cells from mice infused with BrdUrd for 24 or 28 hr. Whereas lymphoma cells from mice treated with 3.3 mg BCNU per kg exhibited 31.2 +/- 3.9 (S.E.) SCEs in second-division cells and 4.7 +/- 0.4 reciprocal and 22.9 +/- 2.0 nonreciprocal SCEs in third-division cells, a 5 times higher dose of BCNU was required to induce similar levels of 30.0 +/- 0.8 SCEs in second-division cells and 4.4 +/- 0.6 reciprocal and 22.6 +/- 1.2 nonreciprocal SCEs in third-division normal cells. BCNU dose-dependent increases in SCE frequencies were also observed following injection of BCNU 8 hr after the start of BrdUrd infusion. The unexpectedly higher levels of SCEs for both normal and lymphoma cells by this treatment protocol may be due to SCEs occurring at the same site in successive divisions in BrdUrd. Regardless of the protocol used, lower nonreciprocal SCE frequencies were observed in third-division cells relative to SCE frequencies in second-division cells; a possible consequence of the cytotoxicity of BCNU. Injection of BCNU produced significant changes in the proportions of normal and lymphoma cells completing one, two, and three or more divisions in BrdUrd. Lymphoma cells were consistently more sensitive to the specific type(s) of BCNU-induced damage leading to SCEs and cell death than were normal cells. These studies indicated that differences in SCE response were not due to cell cycle time, time of drug administration, or potential for repair. It is therefore suggested that increased sensitivity of lymphoma versus normal cells may be due to increased cellular uptake of BCNU.

Animals↗
PubMed1981

Multicellular in vivo sister-chromatid exchanges induced by urethane.

Following urethane inhalation exposure, clear dose--response relationships were apparent in all cell types examined in hepatectomized and intact mice. At concentrations of 0.1 mg/l and higher, induced SCE frequencies were linearly related to log urethane concentrations. No significant differences in SCE response between like cell types of hepatectomized and intact mice were apparent. In hepatectomized mice, there was no significant difference in the SCE response of regenerating liver and alveolar macrophage cells. However, bone-marrow response was significantly lower (p = 0.01). Likewise, in intact mice bone marrow response was significantly lower than in alveolar macrophages (p = 0.01). Inhalation and intravenous infusions of the same total dose of urethane (193 mg/kg) administered over a 4-h period produced comparable SCE responses in all cell types. However, a single intraperitoneal injection of 193 mg/kg just prior to BrdU infusion produced significantly higher SCE frequencies in bone marrow (alpha = 0.01), and alveolar macrophages (alpha = 0.05) of intact mice than did the equivalent inhalation dose. Intraperitoneal injections produced similar results in 2-month-old mice as in 4-month-old mice. However, regardless of the route of administration SCE frequencies in regenerating liver and/or alveolar macrophages were significantly higher than in bone marrow.

Aerosols↗
PubMed1981

Chromosomal methods in population studies.

A brief description of chromosome aberrations and sister chromatid exchange (SCE) as cytogenetic endpoints for evaluation of DNA damaging agents is presented. Problems associated with the use of cytogenetic assays as population monitors of radiation and chemical exposures are discussed. Adequate cell sample size requirements and accurate assessment of cummulative exposure effects with increasing age are stressed as important considerations for reliable cost-benefit analysis of population studies involving low level exposures. Examples of population studies using SCE as an indicator of specific chemical exposures are cited, and factors contributing to variations in control baseline SCE levels are discussed. Possible implications of population cytogenetic data on general public health are suggested.

Chromosome Aberrations↗
PubMed1981

Potency of some carbamates as multiple tissue sister chromatid exchange inducers and comparison with known carcinogenic activities.

The ethyl, ethyl N-hydroxy, isopropyl, and methyl esters of carbamic acid were examined for their abilities to induce sister chromatid exchanges (SCEs) in alveolar macrophages, bone marrow, and regenerating liver cells of C57BL/6J X DBA/2J F1 mice. The relative potencies in inducing SCE, ethyl greater than ethyl N-hydroxy- greater than isopropyl, paralleled previously described activities for induction of lung adenomas in strain A mice. The noncarcinogenic methyl carbamate was inactive in the SCE assay. Relative to bone marrow, regenerating liver and alveolar macrophage cells demonstrated increased susceptibility to carbamate-induced SCE. Of all carbamates studied, only the directly active compound, ethyl N-hydroxycarbamate, produced distinctly different responses in extrahepatic tissues of hepatectomized and intact mice. In intact mice, SCE levels induced by ethyl carbamate in bone marrow and alveolar macrophage cells were not significantly different whether assay followed the last of 12 (three times weekly) serial injections of 2.2 mmol/kg each or after a single injection of 2.2 mmol/kg. Linear regression relationships of log ethyl carbamate versus log SCE or log adenoma response were found to be parallel with the two assays having similar sensitivities.

Animals↗
PubMed1979

Sister chromatid exchange in murine alveolar macrophages, regenerating liver and bone marrow cells--a simultaneous multicellular in vivo assay.

Differential labeling of sister chromatids was achieved simultaneously in murine alveolar macrophages, regenerating liver, and bone marrow cells of partially hepatectomized mice as well as in alveolar macrophages and bone marrow cells of nonhepatectomized mice. The mean frequency of SCE/cell +/-S.D. and the percentage of second division cells for each cell type were determined. No significant differences in mean frequencies of SCE/cell were observed among the cell types or between hepatectomized (alveolar macrophages--3.6+/-2.2, bone marrow--3.4+/-2.2; regenerating liver--3.6+/-2.4) and nonhepatectomized (alveolar macrophages--3.4+/-1.9; bone marrow--2.9+/-1.8). Although the percentage of second division cells was dependent upon cell type, no significant differences were apparent between hepatectomized (alveolar macrophages--57+/-8%; bone marrow--37+/-6%; regenerating liver--65+/-6%) and nonhepatectomized mice )alveolar macrophages--53+/-6%; bone marrow--36+/-4%). Comparisons between BrdU treated and nontreated nonhepatectomized mice revealed no significant alteration in mitotic yields.

Animals↗
PubMed1978

Comparisons of in vivo BrdU labeling methods and spontaneous sister chromatid exchange frequencies in regenerating murine liver and bone marrow cells.

BrdU and BrdC have been employed as DNA labeling agents for differentiation of sister chromatids and for extension of sister chromatid exchange (SCE) methods to regenerating murine liver cells in vivo. Comparisons were made between bone marrow and liver cells isolated simultaneously from mice following DNA labeling with either BrdC or BrdU. Although the total mitotic yield of bone marrow cells was considerably greater than in liver, a higher percentage of second division metaphases was observed in liver cell preparations. The percentages of second division c-metaphase cells observed were 31.5% in bone marrow and 73% in liver cell preparations. Utilizing either BrdU or BrdC, no significant difference in percentage of second division metaphases was discerned. The number of spontaneous SCEs per cell was distributed according to the Poisson probability function. No significant differences in mean numbers of SCEs per cell were found in comparisons of bone marrow (1.40) and liver cells (1.65) or of cells which had incorporated BrdU or BrdC.

Animals↗