PubMed Health⌕ Search

Biomedical subjects

M T Conconi

Publications and source records attributed to M T Conconi.

25 records · Page 2Linked to original sources
PubMed1994

Growth, morphology, and morphometry of human hypertrophic prostate cells treated with suramin in vitro.

This work studies the effects of suramin on the growth and morphology of cell strain U285, obtained from human prostate hypertrophic tissue and cultured in vitro. The FRAME cytotoxicity test was performed to evaluate the inhibition of growth induced by suramin. Cells were exposed to suramin at the time of seeding and 24 hours later; neutral red was added with and without suramin. An optical microscope connected to a computer-aided system and a scanning electron microscope were used to study morphological changes induced by suramin. Growth inhibition depends on drug concentration and exposure period. Moreover, the effect of suramin on neutral red uptake is reversible. Suramin 1,000 microM causes the cells to become spheroid, and they fail to form a monolayer. Our data indicate that the addition of suramin during the lag phase decreases the rate of cell proliferation.

Cell Division↗
PubMed1992

Biological properties of some benzopsoralen derivatives.

The biological activity of some benzopsoralen derivatives, prepared with the aim of obtaining new drugs for photochemotherapy, has been studied. The more interesting compounds are 4-hydroxymethyl-4',5'-benzopsoralen and 4-hydroxymethyl-4',5'-tetrahydro-benzopsoralen, which were found to be active in the dark also: DNA and RNA synthesis were both inhibited in Ehrlich cells, even if in a partially reversible fashion, while protein synthesis remained unaffected. In Chinese hamster ovary cells cultured in vitro, the clonal growth was strongly inhibited by incubation in the dark with both drugs, while a number of chromosomal aberrations was observed in the fraction of growing cells. Using alkaline elution, DNA strand breaks were detected. In addition, in the presence of aphidicolin, a specific inhibitor of DNA polymerase, the clonal growing capacity was completely restored; in contrast, the number of DNA strand breaks remained unchanged. All these results suggest that DNA topoisomerases are probably the target of these two benzopsoralens. These compounds are also good sensitizers; by UV-A irradiation they have a good capacity to produce singlet oxygen, but they appeared to be unable to induce erythemas on guinea-pig skin. Under UV-A light, they induced a strong inhibition of DNA synthesis in Ehrlich cells. Thus, benzopsoralens appear to be capable of inducing strong antiproliferative effects by two different mechanisms, by UV-A irradiation and in the dark.

Animals↗
PubMed1991

Photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen.

The photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen (AcPso), proposed for the photochemotherapy of some skin diseases, were investigated. The photoreaction of AcPso with DNA is weaker in the presence of air than in a nitrogen atmosphere, in terms of total photobinding and DNA cross-linking; when UVA irradiation is performed in air, AcPso behaves as a monofunctional reagent. The quenching effect of oxygen is related to the high capacity of AcPso to produce singlet oxygen. Furthermore, it is demonstrated that AcPso photoadducts are better producers of singlet oxygen than free AcPso in solution. Using DNA sequencing methodology, two modes of DNA photosensitization by AcPso are shown, these lead to the formation of photoadducts mainly at T residues (and at C to a lesser extent) and to photo-oxidized G residues probably via singlet oxygen. Chemical or enzymatic cleavage were used as probes in these experiments. A rapid assay for the detection of the photodynamic effect of a photosensitizer on DNA, involving oxygen, is also described. Finally, the cytotoxicity and genotoxicity of AcPso on E. coli WP2 cells appear to be related to its ability to form photoadducts, in particular cross-links, rather than to its capacity to produce singlet oxygen.

Animals↗
PubMed1986

Photobiological activity of certain pyranocoumarin derivatives: potential agents for the photochemotherapy of psoriasis.

The photobiological properties of a series of pyranocoumarin derivatives having linear (xanthyletines) and angular structure (seselins) have been studied; while the linear derivative carrying the methyl geminal group, typical of the parent natural compound, appeared to be entirely inactive in all tests performed, very probably because of the steric hindrance in the dark interaction with DNA, 4 substances lacking in this group showed a marked capacity for inhibiting DNA synthesis in Ehrlich cells. In particular, 4,6-dimethyl-8-desmethylseselin proved to be about 7 times more active than 8-MOP. Practically all compounds were capable of inducing cross-links in DNA, but this feature, marked in the linear compounds, is very much reduced in the angular ones; this property appears to be clearly related to the mutagenicity in the light and with the skin phototoxicity, which are both marked in the former and low or absent in the latter. In the dark, while all compounds are non-mutagenic in the absence of metabolic activation, in the presence of microsomial enzymes pyranocoumarins become mutagens; only the xanthyletine derivative carrying a geminal methyl group at the 8 position was not activated, suggesting that the enzymes metabolize the pyranic ring.

Animals↗
PubMedDate not supplied

Fibroblast-keratinocyte co-cultures in vitro: growth, morphometry and nutrient exchange.

The interaction between fibroblasts and rat keratinocytes co-cultured in vitro was examined. The epidermal cells cultured with a basal medium or with a conditioning medium (derived from fibroblast cultures) presented a lower growth rate and significantly greater cellular dimensions than those cells grown in the presence of a feeder layer. Qualitative and quantitative differences in the keratin patterns of the cells grown in the three cultural conditions were found. Keratinocytes cultured with the feeder layer expressed seven keratin types (58, 57, 53, 52, 50, 48 and 45 kDa), those with conditioning medium, five types (58, 53, 52, 48 and 45 kDa) and those with basal medium, only one type (45 kDa). This data confirms the dependence of keratinocytes on fibroblasts. HPLC analysis of the culture media, suggested that a protein factor (MW approximately 65 kDa) was secreted by fibroblasts into the culture medium. This factor was added to the keratinocyte culture medium (conditioning medium), and, after a 48 hour culture, was apparently completely removed from the medium by the keratinocytes. Moreover, the keratinocytes cultured with the feeder layer and exposed to indomethacin, a cyclo-oxygenase inhibitor, showed a decrease in growth rate at drug concentrations of < or = 10 microM which did not induce a reduction in the viability of the fibroblasts and keratinocytes in separate cultures. This preliminary data suggests a relationship between fibroblast PGE2 secretion and keratinocyte growth.

3T3 Cells↗
PubMedDate not supplied

Interaction between keratinocytes and fibroblasts cultured in vitro: morphology, morphometry and growth.

In order to elucidate the interactions between fibroblasts and keratinocytes co-cultured in vitro, the morphology and growth of rat keratinocytes cultured with and without a feeder layer were compared. Morphological analysis was coupled with a simple morphometric method of image analysis performed with a computer aided system to demonstrate statistically significant differences between keratinocyte cultures obtained with and without a feeder layer. Epidermal cells cultured without fibroblasts but with a conditioning medium showed a slower growth rate and significant a greater cellular dimensions in comparison with cells grown in the presence of a feeder layer. These results suggest that the conditioning medium induces a morphological change of keratinocytes. The electrophoretic patterns of proteins extracted from cells cultured with and without a feeder layer were identical, whereas densitometric analysis revealed that the quantitative expression of proteins was clearly different. These data confirm that of keratinocyte growth is dependent on fibroblasts or fibroblast products.

Animals↗