Effects of griseofulvin on the morphology, growth and metabolism of fibroblasts in culture

Abstract

Griseofulvin was tested for its effects on the morphology, proliferation and metabolism of fibroblasts cultured from normal human skin and on established lines of mouse fibroblasts 3T3 and 3T6. In all cells treatment produced slight increases in the mitotic index compatible with transient mitotic arrest, but cultures of 3T3 and 3T6 cells also included high proportions (up to 25%) of abnormal multinucleate cells not present in human strains. The proliferation of all cell strains over a 2 or 4 day period was inhibited in proportion to dose (2--17 microgram/ml) with 50% inhibition of growth in the range of 5--11 microgram/ml. Acid mucopolysaccharide secretion was depressed by about 20% at 4--17 microgram/ml. Total protein synthesis was depressed in 3T6 and in human cells, but there was no specific effect on collagen synthesis or secretion.

Effects of corticosteroids on the proliferation of normal and abnormal human connective tissue cells

“…The effect of the corticosteroids at 10 /(g/ml on cell proliferation is summarized in Table i. As in earlier tests on foreskin fibroblasts from normal juvenile donors (Priestley, 1978) there was a contrasting effect on the normal cells: proliferation of HSF8 and HSFio strains was stimulated by hydrocortisone and betamethasone valerate, while clobetasone butyrate had no significant effect or inhibited growth and clobetasol propionate inhibited proliferation in all four strains. Differences in the response of the individual strains within the group were common and often statistically significant: for instance all four pairs of figures for HSFio and HSF12 differ significantly (P<o 01), as do those for HSF8 and HSFio (P<0 05).…”

“…Cells were grown in Nunc plastic flasks in Dulbecco-Eagle medium with 10% fetal calf serum (Gibco-Biocult Ltd, Paisley) and antibiotics at 37 C as previously described (Priestley & Brown, 1978, 1979.…”

“…The method was slightly different from that used in our earlier study of corticosteroids (Priestley, 1978). On day 0, twenty four flasks (growth area 25 cm^) were seeded with ahquots of about i x ioĉ ells.…”

“…Medium collected on day 6 of a proliferation test on SD6 cells was prepared for acid mucopolysaccharide assay by dialysis, concentration and protein precipitation, as previously described (Priestley & Brown, 1978), and uronic acid in protein-free supernatants was measured using m-hydroxydiphenyl reagent (Blumenkrantz & Asboe-Hansen, 1973) with a glucuronolactone standard. Material in unused medium was also assayed for calculation of output per culture, and output per 10'' cells was calculated using day 6 cell counts.…”

“…The relationship, though useful, appears to be fortuitous. It is now clear that L-929 fibroblasts are far more sensitive to inhibition by corticosteroids than fibroblasts from normal human skin, which are not necessarily inhibited at all (Castor, 1962;Kirk & Mittwoch, 1977;Runikis, McLean & Stewart, 1978;Priestley, 1978), but it is still possible that L cells model the response of some abnormal human fibroblasts {Kirk & Mittwoch, 1977). In this paper we examine the behaviour of cells recently isolated from abnormal human skin and connective tissue.…”