Mutagenicity of 3 structurally related epoxides, with defined stereochemical configuration, in Saccharomyces cerevisiae and in V79 Chinese hamster cells.

3 structurally related epoxides, 3,4-epoxycyclohexene, trans-1,2,3,4-diepoxycyclohexane and trans-3,4-epoxycyclohexane-r-1,trans-2-diol (anti isomer) were tested for their ability to induce both point mutation, mitotic gene conversion and recombination in a diploid strain (D7) of the yeast Saccharomyces cerevisiae, with and without a mammalian microsomal activation system, and the formation of 6-thioguanine-resistant mutants in V79 hamster cells. Genetic effects were related to the alkylating properties of the epoxides, as measured by alkylation of 4-(p-nitrobenzyl)pyridine (NBP). Of the 3 epoxides, only 3,4-epoxycyclohexene, characterized by the highest reactivity towards NBP, induced all genetic effects in both test systems. A marginal activity was shown by trans-1,2,3,4-diepoxycyclohexane only in the yeast. The lack of genetic activity of the anti isomer of 3,4-epoxycyclohexane-1,2-diol, in spite of the formal similarity of its functional groups with those present in mutagenic polycyclic arene epoxydiols, was attributed to the dramatic reduction of lipophilicity of the molecule.

Laminin-induced retinoblastoma cell differentiation: possible involvement of a 100-kDa cell-surface laminin-binding protein.

Gene and protein expression of Y-79 retinoblastoma cells growing on poly(D-lysine) is switched from a photoreceptor-like to a conventional neuron-like pathway by the basement membrane glycoprotein laminin. Unlike other cell systems where laminin influences differentiation, Y-79 cells can neither attach to nor chemotactically respond to laminin. However, laminin increases attachment to poly(D-lysine). The laminin effects therefore seem to occur via an adhesion- and chemotaxis-independent mechanism. Moreover, these tumor cells do not exhibit high-affinity laminin binding, having only a single binding site of intermediate affinity. Laminin-Sepharose affinity chromatography of Y-79 cell surface proteins labeled with 125I revealed a single major radiolabeled 100-kDa protein eluted by 20 mM EDTA, with an electrophoretic behavior different from that of integrins. No other proteins were eluted under more stringent conditions. This material, which we call LBM-100 (100-kDa laminin-binding molecule), may be a "differentiative" laminin-binding protein through which laminin influences gene expression and development independently of attachment.