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The cover image, by G. Miolo et al., is based on the Original Article 4,6,4'‐trimethylangelicin shows high anti‐proliferative activity on DU145 cells under both UVA and blue light, DOI 10.1111/cpr.12430. [Image: see text]

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 ofor = 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.

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.