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Copyright of Zeitschrift Für Krebsforschung Und Klinische Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift Für Krebsforschung Und Klinische Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift Für Krebsforschung Und Klinische Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift Für Krebsforschung Und Klinische Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The binding of some mouse skin metabolites and related derivatives of the tumor initiator 7,12-dimethylbenz[a]-anthracene (DMBA) was investigated by P-postlabeling analysis after its topical administration. DMBA and -3,4-dihydro3,4-dihydroxy-DMBA (DMBA-3,4-dihydro-diol) both led to the formation of four DNA adducts, which showed a very similar pattern of spots on thin-l ayer chromato-grams. With -8,9-Ktihdbro-8,9-dihydroxy-7,12-dimethyl-benz[a]anthracene (DMBA-8,9-dihydrodiol) one major adduct was obtained which was chromatographically indistinguishable from one of the DMBA adducts. In contrast, 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA) gave rise to two major adducts which were separable from DMBA adducts. 3-hydroxy-7, 12-dimethyIbenz[a]anthra-cene (3-OH-DMBA) and 7,12-dimethylbenz[a]anthracene-7, 12-epoxide (DMBA-O2) did not lead to detectable amounts of adducts. Quantitative determination of DNA binding showed that an initiating dose ( = 100 nmol) of DMBA yielded ˜12 adducts/10 normal nucleotides. Adduct formation with the same dose of DMBA-3,4-dihydrodiol was 7-8 times higher. At a 4-fold higher dose level, DMBA-8,9-dihydrodiol exhibited a 3- to 6-times weaker binding and 7-OHM-12-MBA a slightly stronger binding than DMBA. Chromatography of the DMBA and DMBA-3,4-dihydrodiol adducts with a solvent containing borate showed a decreased mobility of two out of four adducts in each case. These adducts were also sensitive to oxidation by periodate. The results suggest that two DMBA adducts carried vicinal -hydroxyl groups and thus were probably derived from the 3,4-dihydrodiol1,2-oxide(s) of DMBA. The other two adducts were probably derived from the -stereoisomer(s). When the DNA-modifying capabilities and initiating activities of the more prominent mouse-skin metabolites are considered in relation to DMBA, DMBA-3,4-dihydrodiol is postulated to be a proximate and DMBA-3,4-dihydrodiol-1,2-oxide(s) to be ultimate initiators. [ABSTRACT FROM PUBLISHER]

Specific binding of [H]phorbol-12,13-dipropionate ([H]PDPr) to a participate fraction of mouse skin is demonstrated ( = 35 nM; R = 1.2 pmol/mg protein). A series of compounds of the diterpene ester, indole akaloid and polyacetate types with different degrees of activity as skin tumor promoters and/or irritants have been tested for their capacity to inhibit specific [H]PDPr binding. Three main categories are found: (i) compounds which exhibit a positive correlation between their potency as irritants and promoters and their inhibition of specific binding : 12-O-tetradecanoyiphorbol-13-acetate, 3-O-tetradecanoylingenol, pimelea factor P, ‘teleocidin’, dihydroteleocidin B, and iyngbyatoxin are active and , whereas phorbol and ingenol are inactive and 4-O-methyl-12-C)-tetradecanoyl-phorbol-13-acetate is weakly active; (ii) compounds which are strong irritants and inhibitors of binding but are weak or practically non-promoters: mezerein, 12-O-retinoylphorbol-13-acetate and milliamine C; (iii) strong irritants which are weak or marginally active inhibitors of binding: debromoaplysiatoxin and resiniferatoxin. Some consequences of these findings with respect to interpretations of the biochemical mechanism(s) of tumor promotion are discussed. [ABSTRACT FROM PUBLISHER]

This long-term prospective follow-up study showed that in cryptorchid patients a significant correlation exists between the number of germ cells at the time of orchiopexy (prepuberty) and the spermiogram, and thus a biopsy has a prognostic value. Fifty percent of our patients had a germ cell count of less than 0.1 per tubule and belong to the risk group for sterility. Successful surgery could not induce a significant increase of germ cells in the risk group, although it does prevent secondary testicular damage. Patients with cryptorchidism developed after birth have significantly better chances of fertility than those with primary cryptorchidism. The priming effect of testosterone in the first months of life is important for male fertility. In patients belonging to the risk group treated with buserelin, a significant age-dependent increase in germ cell count occurred. [ABSTRACT FROM AUTHOR]

Sixteen ‘doxy’ spin-labeled 12, 13-(acetate, acylates) of phoebol were assayed in NMRI mice for irritant and for tumor-promoting activity. The spin-labeled positionally isomeric (, )PA-and AP(, )-type esters carry straight aliphatic acyl chains of different overall lengths (number of C atoms). Within the chains the ‘doxy’ label is located in different positions (). The potency of some of the esters as irritants and as promoters is comparable to or even higher than that of the prototype diterpene ester promoter 12--tetradecanoylphorbol-13-acetate and its positional isomer 12--acetylphorbol-13-tetradecanoate. Their irritancies on the ear and their promoting activities on the back skin depend strongly on the structural features of the acyl chain carrying the spin label. Based upon the bioactivities of individual esters biologically meaningful probes were defined for investigations of the molecular interaction of phorbol-ester-type promoters with cellular targets for electron paramagenetic resonance. [ABSTRACT FROM PUBLISHER]

From the roots of Euphorbia cyparissias L. a highly irritant diterpene ester fraction was isolated and further resolved into its constituents. Together with some less active and some inactive isomers, the pure Euphorbia factors were characterized as new diesters of 13-hydroxyingenol and as triesters of the new 13,19-dihydroxyingenol. The Euphorbia factors Cy, Cy and Cy are the strongest irritants of the ingenane ester type hitherto known, Cy being at least as active as the standard diterpene ester type irritant 12-O-tetradecanoylphorbol-13-acetate (TPA). [ABSTRACT FROM AUTHOR]

From the roots of Croton flavens L., 3 highly irritant and tumor promoting Croton factors F- F and the corresponding 3 cryptic Croton factors F′- F′ 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. [ABSTRACT FROM AUTHOR]