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T Regan

Publications and source records attributed to T Regan.

29 records · Page 2Linked to original sources
PubMed1985

Effects of diethylstilboestrol-dipropionate on SCEs, micronuclei, cytotoxicity, aneuploidy and cell proliferation in maternal and foetal mouse cells treated in vivo.

The effect of diethylstilboestrol-dipropionate on the frequency of SCEs and micronuclei, cytotoxicity, aneuploidy and cell proliferation rates of foetal liver and maternal bone marrow cells following exposure of pregnant mice was measured. An increase in the number of aneuploid and polyploid cells was observed in both tissues. There was no effect on micronuclei frequency, SCE frequency, or cell proliferation rate.

Abortion, Spontaneous↗
PubMed1984

Sister-chromatid exchange and micronucleus induction as indicators of genetic damage in maternal and foetal cells.

The effectiveness of 3 compounds, procarbazine, mitomycin C and cyclophosphamide as inducers of sister-chromatid exchanges (SCEs) in granulocyte-macrophage progenitor cells, in foetal liver and bone marrow from pregnant mice at day 17 of gestation were determined. Cyclophosphamide and procarbazine induced similar SCE frequencies in maternal and foetal cells. Mitomycin C was slightly less effective in foetal liver than in maternal bone marrow. In contrast to the results of SCE induction, cyclophosphamide produced more micronucleated polychromatic erythrocytes in foetal liver than in bone marrow. The SCE results for mitomycin C and procarbazine are compared with results obtained previously for micronuclei induction in 15-day pregnant animals.

Animals↗
PubMed1983

Short-term tests for transplacentally active carcinogens. Induction of sister-chromatid exchanges in foetal brain, lung and blood-forming cells by procarbazine and cyclophosphamide.

The induction of sister-chromatid exchanges (SCEs) by cyclophosphamide (CP) and procarbazine (PC) in mouse granulocyte-macrophage precursor cells (GM cells) and erythroblasts from foetal liver, and cells from foetal brain and foetal lung has been measured. Agents were administered in vivo, and cells explanted into BrdUrd-containing medium for 2 cell cycles in vitro (using specific growth-promoting substances where necessary) to determine SCE frequency. Tissue and cell-type differences in responses were observed, and it is concluded that the in vivo/in vitro transplacental SCE technique is a useful indicator of genotoxic effects of agents which are potential transplacental carcinogens.

Animals↗
PubMed1983

Short-term tests for transplacentally active carcinogens. A comparison of sister-chromatid exchange and the micronucleus test in mouse foetal liver erythroblasts.

The effectiveness of 6 chemicals (benzo[a]pyrene, (BaP), cyclophosphamide (CP), diethylnitrosamine (DEN), methyl methanesulphonate (MMS), mitomycin C (MC) and procarbazine (PC) ) as inducers of micronuclei in foetal liver and maternal bone marrow erythroblasts has been determined, and related to that of gamma-radiation. CP, DEN, MMS and PC were all more effective in the foetal liver. The induction of micronuclei and SCEs by each chemical in foetal erythroblasts after in vivo exposure was measured. When expressed as induction of sister-chromatid exchanges (SCEs) per erythroblast/induction of micronuclei per erythroblast (/microM/kg), the ratios obtained were MC 580, BaP 470, DEN 430, CP 258, MMS 140 and PC 13. The lowest doses detected as potentially genotoxic by each test in foetal liver erythroblasts are (with the exception of PC which is a relatively ineffective inducer of SCEs) similar. When isolated foetal livers were exposed in vitro, SCE dose responses to BaP, MC, MMS and PC could be directly related to those from in vivo exposure, indicating the role of the foetal liver in metabolic activation, but CP was considerably more cytotoxic. The transplacental micronucleus test, and in vivo/in vitro method for SCEs in foetal liver erythroblasts, provide sensitive, complementary assays for genotoxic effects of chemicals during prenatal life. Since foetal liver possesses greater metabolic potential than adult bone marrow, the transplacental tests respond to genotoxic agents not detected by bone-marrow systems.

Animals↗
PubMed1977

Regulation of pre-natal haemopoiesis: evidence for negative feedback control of erythropoiesis in the foetal mouse.

The effects of medium conditioned by erythrocytes on in vitro differentiation of mouse prenatal erythroblasts were examined. Haem synthesis was inversely proportional to the concentration of erythrocyte-conditioned medium (ECM) in either presence or absence of erythropoietin (EP), but concentrations of ECM which limited haem synthesis to 50% of normal had no effect on changes in erythroblast numbers. ECM reduced uridine incorporation into RNA and limited the rise in incorporation due to stimulation by EP. ECM enhanced thymidine incorporation into DNA. This enhancement was additive with that due to EP, but appeared earlier. Thymidine labelling indices of liver cells were not changed by ECM in vitro. Serum from polycythaemic animals limited haem synthesis by EP stimulated foetal liver cells in vitro. These observations provide evidence for susceptibility of foetal liver erythroblasts to negative feedback control of differentiation, dependent on the concentration of circulating erythrocytes. Characteristic changes in kinetics of prenatal erythropoiesis in vivo can also be related to increasing erythrocyte concentration.

Animals↗
PubMed1976

Haemopoietic progenitor cells in prenatal congenitally anaemic 'flexed-tailed' (f/f) mice.

The incidences of erythroid colony forming cells (CFUe) and granulocyte-macrophage colony forming cells (CFUc) have been measured in 11-18 d prenatal livers of mice of genotype f/f and nearly congenic +/+ controls. In normal fetal livers numbers of CFUe (cells able to form colonies of 16 or more cells after 72 h in vitro) rise to a maximum on day 14 of gestation and represent c 1% of total fetal liver cells. In f/f fetal livers, peak values for numbers and proportions of CFUe are 50% of normal. The f/f lesion does not reduce the numbers of CFUc in fetal liver. Since this deficiency in CFUe parallels deficiencies of similar magnitude in spleen-colony forming units (CFUs) and erythroblasts in the liver, and erythrocytes in the blood, of f/f fetuses it is concluded that the f/f lesion is expressed at an early stage of haemopoietic development in prenatal life. The possibility that restricted haem synthesis is the primary effect of the f/f genotype and responsible for disturbances of both haemopoietic cellular proliferation and haemoglobin synthesis is examined.

Anemia↗
PubMed1975

Expression of congenital defects in the haemopoietic micro-environment. Erythroid and granulocyte-macrophage progenitor cells in pre-natal 'steel' (Slj/Slj) anaemic mice.

The erythropietin sensitivities of dissociated cell cultures and explanted fragments of fetal livers of congenitally anaemic Slj/Slj mice, and their normal littermates, have been compared. The erythropoietin responsiveness of Slj/Slj foetal liver cells is deficient in both types of culture. The maximum liver complement of erythroid colony forming cells (CFUe) occurs on the 16th day of development when 'normal' livers contain approximately 6 X 10(5) erythroid colony forming cells/liver. In Slj/Slj fetuses the maximum reached is only 1 X 10(5). Granulocyte-macrophage colony forming cells (CFUc) in Slj/Slj fetal livers are also reduced to approximately 60% of normal numbers. Erythroid colony forming cells are also reduced in the spleen and femoral bone marrow of Slj/Slj mice in the 2-3 days preceding birth. Granulocyte-macrophage colony forming cells are rare in the femoral marrow of pre-natal Slj/Slj mice, but their production in the Slj/Slj pre-natal spleen appears unaffected.

Anemia↗
PubMed1975

The relationship between erythropoietin-dependent cellular differentiation and colony-forming ability in prenatal haemopoietic tissues.

Levels of haem synthesis achieved by foetal liver erythroblasts responding to erythropoietin in vitro are similar in dissociated cell cultures and in cultures of organized tissues. Erythroid colony-forming cells reach maximum numbers on the sixteenth day of gestation. Their presence in foetal liver is associated with the period of most rapid production of erythrocytes, and with in vitro sensitivity to erythropoietin measured as enhanced haem synthesis. It is concluded that at least a proportion of erythroid colony-forming cells in the foetal liver are dependent on erythropoietin in situ and that these cells are separated from the earliest recognizable pro-erythroblast by 1-2 cell divisions. Populations of granulocyte-macrophage colony-forming cells change independently of erythroid colony-forming cell numbers.

Animals↗