Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge ( Euphorbiaceae )

Abstract

Special procedures were developed to investigate poisonous milk of lactating goats fed experimentally on aerial parts of the herb Euphorbia peplus L. In extracts of the milk, weakly irritant in the mouse-ear assay, three diterpene ester toxins were detected by techniques of high-performance liquid chromatography. They are of the ingenane structural type: Euphorbia factor Pel (ingenol 20-acetate 3-angelate), Euphorbia factor Pe2 (20-deoxyingenol 3-angelate) and Euphorbia factor Pe4 (20-deoxyingenol-6alpha,7alpha-epoxide 3-angelate). From goats milk collected 15 days after cessation of the experimental feeding period, extracts were completely free of diterpene ester toxins. The toxins polluting the milk are identical to diterpene ester entities occurring in the aerial parts of E. peplus. Of these, Euphorbia factors Pel and Pe2 are known as promoters of tumors of mouse skin. Apart from the toxic Euphorbia factors, the non-toxic parent alcohol ingenol was also detected in the milk. It is absent in the plant, and may have been generated metabolically from a certain portion of the toxic diterpene esters picked up by the goats from their fodder. The results presented here provide, for the first time, data for a novel interpretation of the locally high incidence of esophageal cancer observed in certain areas in the Caspian littoral of Iran, associated with a greater consumption of goat's (and sheep's) milk.

Contact with ruminants is associated with esophageal squamous cell carcinoma risk

“…An early nutritional study showed higher consumption of sheep’s and goat’s milk in northern Iran than in lower risk areas 18 . Another study showed that milk of small ruminants fed by a family of Euphorbiaceae flower plants contained diterpene esters, a group of compounds which showed promoting activity in experimental systems 19 . This genus is one of the most species-rich flowering plants, and several of its species occur in the study area 20 .…”

Identification of Daphne genkwa and Its Vinegar-Processed Products by Ultraperformance Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry and Chemometrics

“…Eight compounds in the methanol extracts were identified as major contributors to the differences between CHDG and VPDG: apigenin-7- O -β- d -methylglucuronate (a), hydroxygenkwanin (b), genkwanines O (c), orthobenzoate 2 (d), tiliroside (e), quercetin (f), caffeic acid (g), and naringenin (h). Considering their toxicity [ 48 , 49 , 50 , 51 ], the reduction in the amount of daphnane-type diterpene ester compounds in VPDG might explain the mechanism through which stir-baking with vinegar reduces the toxicity of CHDG. In addition to the aforementioned compounds, other compounds not listed here contributed to the differences between CHDG and VPDG.…”