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Biomedical subjects

E Hecker

Publications and source records attributed to E Hecker.

At least 109 records · Page 6Linked to original sources
PubMed1978

Cocarcinogens of the diterpene ester type from Croton flavens L. and esophageal cancer in Curaçao.

From the roots of Croton flavens L., 3 highly irritant and tumor promoting Croton factors F1--F3 and the corresponding 3 cryptic Croton factors F'1--F'3 were isolated and characterized as novel esters of 16-hydroxy- and 4-deoxy-16-hydroxyphorbol, respectively. These findings suggest that tumor promoters of the phorbol ester type, ingested through the widespread and frequent use of Croton flavens according to local habits, may be causally related to the well recognized high rate of esophageal cancer on Curaçao.

Animals↗
PubMed1978

[Co-carcinogens or modulators of carcinogenesis. New aspects of the etiology of human tumors and of the molecular mechanisms of carcinogenesis].

Within the last 10 years numerous new and typical exogenous cocarcinogens were identified chemically as well as biologically and characterized biochemically as initiation or tumor promoters. They are highly irritant diterpene esters of plant origin. Promoters of this type were recently detected also in the Euphorbiacea Croton flavens L., the multiple use of which for stimulants according to local habits was previously held responsible for the unusually high rate of esophageal cancer on Curacao. This detection confirms for the first time that in the etiology of human cancer besides solitary carcinogens (first-order carcinogenic risk factors) also cocarcinogens of the promoter type have to be considered (second-order carcinogenic risk factors). -- The active principles of the diterpene ester type are the strongest promoters known so far; they are noninitiators and nonmutagens. Of the manyfold biochemical activities of these promoters the three most actual are: the TPA molecule does not require activation by metabolic alteration, it releases very rapidly prostaglandin E2 from cellular membranes and it activates latent DNA-viral genoms.

Animals↗
PubMed1978

Inflammatory, tumor initiating and promoting activities of polycyclic aromatic hydrocarbons and diterpene esters in mouse skin as compared with their prostaglandin releasing potency in vitro.

Release of prostaglandin E2 (PGE2) in cultured peritoneal macrophages of NMRI mice by skin irritant tumor initiators and promoters was investigated. Initiators of the polycyclic aromatic hydrocarbon type, e.g., DMBA, caused slight irritation on the mouse ear but even relatively high doses did not stimulate PGE2-release to any measurable extent within 4 h after administration in vitro. Apparently there is no correlation between irritation and initiating activity in mouse skin and PGE2-release in macrophages. On the other hand, promoters of the diterpene ester type, e.g., TPA, were strong irritants on the mouse ear. Even low doses of these compounds stimulated PGE2-release from macrophages dramatically within 1 h after administration in vitro. Moreover, a good correlation was established between irritant and promoting activity in mouse skin and PGE2-release in macrophages of a series of tigliane, ingenane and daphnane type diterpene derivatives. These results suggest that also in mouse skin PGE2-release may occur following exposure of the target cells to promoters of the diterpene ester type resembling one of the most early molecular events of promotion. This event could initiate both skin irritation and cell proliferation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

New tigliane and daphnane derivatives from Pimelea prostrata and Pimelea simplex.

From the methanol extract of Pimelea prostrata, prostratin (I) and 2 autoxidation products have been isolated. They are tigliane derivatives and relatively nonirritant on the mouse ear. The irritant pimelea factor P5 (IIa) also with a tigliane skeleton and related to mancinellin (IIb), as well as the irritant diterpene ester pimelea factor P1 (IIa, simplexin) with daphnane skeleton, were found to be present in both P. prostrata and P. simplex. Further the irritant homologue of simplexin, pimela factor IIIb was detected in P. prostrata. Some biogenetic consequences of these findings are discussed.

Animals↗
PubMed1977

New highly irritant euphorbia factors from latex of Euphorbia tirucalli L.

From the latex of Euphorbia tirucalli L. growing in Madagascar, 5 new euphorbia factors were isolated. They were characterized as 13-O-acetyl-12-O-acylphorbol- and 12-O-acetyl-13-O-acylphorbol derivatives carrying homologous conjugated unsaturated fatty acids as acyl groups. Furthermore, 2 mixtures of homologous 3-O-acylingenol derivatives are obtained carrying the same type of unsaturated fatty acids. Due to their highly unsaturated acyl groups all Euphorbia factors or factor groups isolated are highly sensitive to autoxidation.

Irritants↗
PubMed1977

Reaction of arene oxides with nucleosides.

Inosine was reacted with phenanthrene-9,10-oxide and 7,12-dimethylbenz(a)anthracene-5,6-oxide (DMBA-5,6-oxide) to yield the corresponding N-1-alkylinosines. They were shown to undergo hydrolysis to 5-amino-4-imidazole-N-alkylcarboxamide ribosides when heated in the presence of sodium carbonate. Guanosine was reacted with DMBA-5,6-oxide to yield a mixture of N-7-alkylguanines along with a smaller amount of an orcine positive product exhibiting an ultraviolet spectrum resembling that of DMBA-5,6-dihydrodiol.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

On the biochemical mechanism of tumorigenesis in mouse skin. VII. The effects of tumor promoters on 3H-choline and 3H-glycerol incorporation into mouse epidermal phosphatidylcholine in relation to their effects on 3H-thymidine incorporation into DNA.

The kinetics of the stimulation of phospholipid and DNA biosynthesis in mouse epidermis after treatment with various tumor promoting agents has been investigated. 3H-choline and 3H-glycerol were used as precursors for phosphatidylcholine. An early stimulation of 3H-choline incorporation into phosphatidylcholine is observed which always precedes the stimulation of 3H-thymidine incorporation into epidermal DNA. This is interpreted as being a manifestation of the proliferation of cellular membranes in preparation for cell division. Appreciable differences are observed in the incorporation of 3H-choline and 3H-glycerol into phosphatidylcholine, the possible reasons for which are discussed. It is concluded that 3H-choline incorporation is a more reliable parameter for the measurement of phosphatidylcholine biosynthesis than 3H-glycerol incorporation. The relationship between those effects on phospholipid synthesis and the tumor promoting activity of the substances tested is discussed.

Animals↗
PubMed1976

Definitions and terminology in cancer (tumor) etiology--an analysis aiming at proposals for a current internationally standardized terminology.

The Committee on International Collaborative Activities (CICA) of the International Union Against Cancer (UICC) has decided to attempt to provide a current international standardized terminology in cancer (tumor) etiology, in cooperation with the International Agency for Research on Cancer (IARC) and the Worlk Health Organization (WHO). As a first stage of this attempt and to encourage international discussion, CICA has requested one of its members, the author, to formulate and publish under his responsibility the present analysis and proposals. The present paper to be published in a number of cancer journals outdates all of its previous versions or drafts.

International Agencies↗
PubMed1975

On the active principles of the spurge family. III. Skin irritant and cocarcinogenic factors from the caper spurge.

The toxic and irritant principles of the seed oil and of the latex of the caper spurge (Euphorbia lathyris L.) were isolated together with several non irritants of similar chemical structure. From the seed oil two irritant Euphorbia factors L5 and L6 and from the latex a mixture of irritant Euphorbia factors were obtained. Euphorbia factor L5 was identified as 3-hexadecanoate of the new tetracyclic, poly-functional diterpene parent alcohol ingenol. Euphorbia factor L6 most probably is the 3-tetradeca-2,4,6,8,10-penta-enoic acid ester of ingenol. The mixture of Euphorbia factors was shown to contain esters of ingenol and of 16-hydroxy-ingenol, respectively, each containing a long chain unsaturated fatty acid, most probably in 3-position. The non irritants from the seed oil comprise ingenol-20-hexadecanoate (compound L4) and several esters of macrocyclic diterpenes of the new lathyrol type (compounds L1-L3, L8, and possibly L7). Compound L4 is a positional isomer of Euphorbia factor L5 and most probably an artefact formed during the isolation procedure. The macrocyclic diterpenes are of interest as possible intermediates in the biogenesis of tetracyclic diterpene parents of cocarcinogenic esters. The parent alcohols ingenol and 16-hydroxy-ingenol are inactive irritants. As compared to croton oil factor A1 (TPA), Euphorbia factor L5 exhibits about 1/10 of its irritant activity on the ear and about 1/10 of its cocarcinogenic activity on the back skin of mice. As an irritant Euphorbia factor L6 shows about 1/5 of the activity of A1. Structure/activity relationships of ingenol and phorbol esters and the possible role of cocarcinogens of plant origin as second order carcinogenic risk factors are discussed.

Animals↗
PubMed1975

Epoxide hydrase activity in mouse skin eidermis.

By fractionation of mouse epidermis a "microsomal" fraction may be obtained with a specific EH-activity at least 6-7 times higher than that of epidermis homogenates. Such enrichment allows to utilize the radioassay with 7--3H-styrene oxide as substrate which normally is too insensitive for organs with low levels of EH-activities. By the procedure developed the unambiguous demonstration of EH-activity in the epidermis of mouse skin is possible.

Animals↗