Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae) V. Skin irritant and tumor-promoting diterpene ester toxins of the tigliane and ingenane type in the herbs Euphorbia nubica and Euphorbia helioscopia contaminating fodder of livestock

Irritant diterpene ester toxins were isolated from Euphorbia nubica and E. helioscopia, which are contaminants of the green fodder of livestock in Egy pt. Fractionations of methanol extracts of aerial parts of both plants were monitored by the irritation unit on the mouse ear. Plant extracts were sub jected to multiplicative distribution methods, yielding irritant hydrophili c fractions that were further purified by column chromatography. Final puri fication of the materials was achieved by TLC (silica gel) followed by HPLC , or by TLC: alone. In this way, from E. nubica, five Euphorbia factors (Nu 1-Nu5) were isolated and characterized as short-chain polyfunctional diterp ene esters of tigliane-type parent alcohols. The two weak irritants Nul and Nu3 were triesters of 4-deoxy(4 alpha )phorbol Nu2 was shown to be a tries ter of the stereoisomeric tigliane-type parent alcohol 4-deoxyphorbol. Weak irritant Nu4 probably is a positional isomer of Nu2. Nu5 was characterized as a short-chain triester of 4,20-dideoxy-5 xi -hydroxyphorbol. From E. he lioscopia, six short- to medium-chain polyfunctional diterpene esters of th e ingenane type, generally containing unsaturated acids were obtained, i.e. , four irritant eaters of ingenol (Euphorbia factors H1, H2, H5, and H6) an d two eaters of 20-deoxyingenol (non-irritant Euphorbia substance HS4, and irritant Euphorbia factor HS). All irritant Euphorbia factors of the tiglia ne and ingenane diterpene eater type described in this investigation are co nsidered to be more or less active tumor promoters, i.e., conditional (non- genotoxic) cancerogens. The Euphorbia factors assayed exhibited moderate (H 1) to low (HS) relative tumor-promoting potency in comparison to the ingena ne prototype DTE tumor promoter 3-TI.