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  • 1
    ISSN: 1432-1335
    Keywords: Key words Conditional cancerogens ; Diterpene esters ; Euphorbia peplus ; Food chain ; Dietary cancer ; Milk polluted ; Skin irritants ; Tumor promoters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothesis was proposed that there is a risk of dietary cancer from conditional cancerogens in produce of livestock polluted with irritants of the diterpene ester type, picked up by feeding on species of Euphorbiaceae ( spurge). To challenge this, several herbaceous plants of the genus Euphorbia, widespread as weeds and contaminants of livestock fodder, were identified botanically and extracts of their aerial parts were tested for irritancy on the mouse ear. As compared to a standard probe of croton oil, the extracts of E.␣peplus, E. nubica and E. helioscopia displayed irritancy. The most active extract (that from E. peplus) was investigated by a fractionation procedure monitored by the mouse ear assay, and five molecularly uniform irritant Euphorbia factors Pe1–Pe5 were identified as diterpene ester-type toxins. Together these factors comprise at least 11 ppm in the aerial parts. They were characterized individually to␣carry the diterpene parent alcohols ingenol, 20-deoxyingenol, and 20-deoxyingenol-6 α, 7α-epoxide. The irritancy of the aerial plant parts was shown to be caused mainly by the Euphorbia factors Pe1 and Pe2 together. Upon chronic administration of these irritants and hyperplasiogens as principal cancerogenic risk factors in the mouse skin initiation/promotion bioassay, Pe1 and Pe2 were established as tumor promoters. These findings together support the␣initial hypothesis and suggest the need for further investigations to determine whether there is a consequent risk of dietary cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 179-185 
    ISSN: 1432-1335
    Keywords: Key words Conditional cancerogens ; Risk of dietary cancer ; Diterpene esters ; Euphorbia peplus ; Food chain ; Lactating goats ; Polluted milk ; Poisoning by contaminated fodder ; Tumour promoters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed with their usual green fodder. During the experimental feeding period they showed symptoms of general poisoning. In necropsy the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. Adverse symptoms in the liver and kidney were also reflected in an alteration of the levels of certain serum enzymes and of blood urea nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids, caused poisoning and even death, with signs similar to those observed in the adult dams. These observations support the hypothesis that the poisoning observed in both milk-raised kids and mother goats is caused by diterpene ester type toxins present in the aerial parts of the herb contaminating the dams fodder. Generally, such skin irritant and hyperplasiogenic toxins are known to be highly active tumour promoters of skin and other organ, e.g. in mice. Lactating goats – as an important source of milk around the world – in a setting similar to that described, may provide a valid experimental etiological model for investigation of food polluted by tumour-promoting diterpene ester toxins.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 301-306 
    ISSN: 1432-1335
    Keywords: Key words Conditional cancerogens ; Diterpene esters ; Euphorbia factors ; Food chain ; Metabolism of␣tumor promoters in goats ; Poisoning by contaminated fodder ; Pollution of goat's milk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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-6α,7α-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 Pe1 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.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 117 (1991), S. 205-216 
    ISSN: 1432-1335
    Keywords: Computerized processing ; Cumulative tumor incidence ; Skin tumors ; Statistical analysis ; Survival rate ; Tumor promotion ; Tumor rate ; Tumor yield
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The initiation/promotion standard protocol 28 (protocol 28), developed and used previously as an experimental model to verify the cancerogenic process of initiation/promotion in mouse skin, was revised in three aspects: (a) statistically it was shown sufficient to use, per promoter dose group, 16 colony-outbred female NMRI mice: (b) by weekly individual records of tumor response (and health status) of each mouse in a dose group, cumulative tumor incidences (and mean and extreme body weights) are determined; from these data the collective records (tumor response, health status), the only data accessible from protocol 28, may be generated in addition; (c) the details of dose groups and all data on tumor response and health status are processed by computer using the program package PAPILLOM. The latter was developed specifically for this purpose, is written in the programming language APL and designed for easy handling by staff of animal laboratories. The program package calculates, from the individual records per promoter dose group, cumulative tumor incidences (and survival data) with confidence limits for any one exposure time, and the package may be linked to programs for statistical validations. In addition, from the collective records it calculates the tumor rates, tumor yields and survival rates for any one exposure time. These data, obtained by either of the standard protocols (16 or 28), are fully comparable. For pure compounds they may be used to calculate semiquantitative tumor-promoting potencies. These values for more than 80 polyfunctional diterpenes of the tigliane, ingenane and daphnane type, scattered in or calculated from previous papers, together with their irritancies, were compiled. Within recent years, computer-assisted standard protocol 16 has been used to handle and evaluate about 1000 promoter dose groups. Protocol 16 allows one to extract and utilize more and better toxicological information on tumor response and health status from any one dose group, utilizing significantly fewer experimental animals than required by protocol 28. Thus, the computer-assisted standard protocol 16 optimizes the utility of the experimental model of mouse skin for the amount, quality and management of experimental data as well as for the requirements of animal protection.
    Type of Medium: Electronic Resource
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