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Biomedical subjects

R Franz

Publications and source records attributed to R Franz.

At least 55 records · Page 3Linked to original sources
PubMed1990

The tentative identification of DNA-adducts generated by trans-4-dimethylaminostilbene and trans-4-acetylaminostilbene in rats.

Tritium-labeled trans-4-dimethylaminostilbene (DAS) and trans-4-acetylaminostilbene (AAS) were administered orally to female Wistar rats. RNA and DNA were isolated from livers after 24 h and 28 days. Hydrolysates were analyzed by gel filtration and HPLC. Total binding to nucleic acids and elution profiles of hydrolysates were very similar for both aminostilbene derivatives. The large polar fraction eluting early in Sephadex LH20 chromatograms accounting for 60-80% of total DNA-bound radioactivity could not be assigned to individual base adducts and most likely is not due to incomplete hydrolysis but rather to cross-links between bases or proteins and bases. Of the total radioactivity bound to nucleic acids 6-7% in RNA and 3-5% in DNA could be tentatively identified as four isomeric, cyclic guanine adducts (predominantly (S,S)- and (R,R)-guanine-N2,beta-N3,alpha-N-acetylaminobibenzyl) by cochromatography with synthetic reference compounds. The most abundant single adduct accounting for 20-30% of RNA-bound radioactivity (fraction G in Sephadex LH20 chromatography) could not be identified. The long-term experiment revealed different persistence of DNA adducts: the polar material decreased to about 2/3, the cyclic guanine adducts (fraction d-B) to about 1/3 to 1/2 within 4 weeks, whereas one of the unidentified DNA-adducts (fraction d-E) persisted completely. AAS labeled in the acetyl group was administered in an additional experiment. The presence of the acetyl group could be demonstrated in most of the adducts, but non-acetylated adducts were found also. The ratio of non-acetylated:acetylated cyclic B-adducts in RNA was 1:2 from DAS and 1:13 from AAS, in DNA 1:3 and 1:10, respectively.

Animals↗
PubMed1988

Reaction of trans-4-N-acetoxy-N-acetylaminostilbene with guanosine and deoxyguanosine in vitro: the primary reaction product at N2 of guanine yields different final adducts.

The model ultimate carcinogen, trans-4-N-acetoxy-N-acetylaminostilbene (N-acetoxy-AAS), was reacted with guanosine (Guo) and deoxyguanosine (d-Guo) and the resulting adducts were purified by Sephadex LH-20 chromatography and HPLC for structure identification. A number of new adducts was identified by mass and 1H-NMR spectroscopy. The generation of all known adducts can now be explained by a common mechanism. The electrophile formed from the hydroxamic acid ester at C-beta reacts in a first step predominantly with N2 of guanine (Gua). The resulting quinone-imide intermediate reacts in a second step with either one of three nucleophiles: (1) predominantly with N3 of Gua to yield the previously described angular cyclic adducts ((5R,6R)/(5S,6S)-9-oxo-5,6,7,9-tetrahydro-imidazo(2,1-b)purines); (2) with N1 of Gua to yield linear cyclic adducts ((6R,7R)/(6S,7S)-9-oxo-5,6,7,9-tetrahydro-imidazo(1,2-a)purines); (3) with water to yield the open ring (1R,2R)/(1S,2S)-2-(N2'-guanyl)-1-hydroxyethanes. To some minor extent (1:8-1:9) the electrophile reacts first with N1 or N3 of guanine which leads to the formation of two pairs of the corresponding regioisomeric cyclic adducts. This reaction mechanism may also explain the formation of cross-links between different bases.

Carcinogens↗
PubMed1988

Synovial oxygen partial pressure after experimental microtraumatic joint affection.

We have developed a method allowing the direct determination of the synovial oxygen partial pressure (pO2) in vivo by using puncture electrodes. The investigations were carried out on the knee joints of young adult rabbits. Immediately after a defined microtraumatization of the left knee joints, there was a decrease in the synovial pO2 down to an average of 72% of an initial value obtained from untreated control animals. But 42 and 84 days after loading, a significant rise in the synovial pO2 was detectable. The unloaded contralateral joints showed a slight consensual reaction. The dynamics of the synovial pO2 after the microtraumatization of joints is under discussion on the basis of results of micromorphological studies of the articular cartilage and the synovial membrane.

Animals↗
PubMed1988

[Allogenic half-joint transplantations].

Reported in this paper are twelve cases of allogenic transplantation of half-joints and quarter-joints, following removal of locally delimited tumours. Three transplants were incorporated with functionally satisfactory result to three patients over a period of seven years. Infections and recurrence of tumours were the most frequent causes of failure of transplantations. These results are discussed together with possibilities of future allogenic half-joint transplantations.

Adolescent↗
PubMed1987

Reaction of trans-4-N-acetoxy-N-acetylaminostilbene with guanosine, deoxyguanosine, RNA and DNA in vitro: predominant product is a cyclic N2,N3-guanine adduct.

The model ultimate carcinogen trans-4-N-acetoxy-N-acetylaminostilbene was reacted with guanosine, deoxyguanosine, RNA and DNA using differently labeled reactants. The nucleoside as well as the deoxynucleoside yielded predominantly four cyclic guanine adducts: (S,S)- and (R,R)-guanine-N2,beta-N3,alpha-N-acetyl-aminobibenzyl and the regioisomers with the N2,alpha-N3,beta-attachment in a ratio of 9:9:1:1. The same adducts predominate in RNA and DNA which demonstrates that guanine reacts most avidly among the bases. The stability of the N-glycosidic bond is quite different between ribosides and deoxyribosides. Under neutral conditions, the riboside derivatives are stable, whereas deoxyribose is cleaved off rather readily. As a consequence DNA depurinizes to some extent during the in vitro reaction and during enzymatic digestion. On the other hand, N2,N3-attachment of the acetylaminostilbene moiety to guanine appears to impair the activity of nucleases for steric reasons. This could explain the incomplete enzymatic hydrolysis of modified nucleic acids. The results provide an important basis for further investigations to identify the nucleic acid adducts generated in vivo.

Animals↗
PubMed1986

Identification of nucleic acid adducts from trans-4-acetylaminostilbene.

It has been proposed that trans-4-acetylaminostilbene (AAS) is an initiator for tumor formation in rat liver and that the metabolically formed hydroxamic acid ester ultimately reacts with nucleic acids in vivo. We have now studied the generation of a major adduct in vitro. trans-4-N-Acetoxy-N-acetylaminostilbene (N-acetoxy-AAS) was reacted with guanosine at pH 7.5 and reaction products were separated by chromatography on Sephadex LH-20 and RP18 HPLC. The major adduct isolated consists of four isomers which have been tentatively identified by mass- and 1H-NMR spectroscopy as (S,S)- and (R,R)-guanosine-N2,beta-N3,alpha-N-acetylaminobibenzyl and the respective regio isomers guanosine-N2,alpha-N3,beta-N-acetylaminobibenzyl. These adducts are formed in a ratio of 9:9:1:1. Under acidic conditions (pH 2) the ribose moiety is removed and two regio isomeric base adducts are formed in the ratio 9:1. Results to be published indicate that the adducts are also formed in vivo in rat liver RNA and DNA.

Animals↗
PubMed1986

Effects of antioxidants and haemoglobin status on the t-butyl hydroperoxide-induced oxygen uptake by red blood cells.

Oxygen uptake by erythrocytes exposed to t-butyl hydroperoxide (t-BHP) exhibited an induction period. The rate of oxygen consumption can be reduced by antioxidants and blood plasma. The induction time was not appreciably modified by the antioxidants tested, however, plasma increased it by a factor of two. The in vivo pretreatment with diethyl maleate (0.6 g kg-1) produced increased rates of oxygen uptake without changes in the induction period, while vitamin E (12.5 mg kg-1) elicited lower oxygen consumption rates and longer induction times, compared to those observed in cells from control rats upon addition of the hydroperoxide. These results suggest that the antioxidants tested on the t-BHP lipid peroxidation in erythrocyte suspensions act as inhibitors and/or retarders of the process. Furthermore, lipid peroxidation induced in these conditions seems to depend upon the haemoglobin status of the cells as oxygen uptake, malondialdehyde production and chemiluminescence were significantly higher in methaemoglobin-containing cells than in those containing oxyhaemoglobin.

Animals↗
PubMed1986

The reduction of aromatic nitro compounds with Zn/Cu. A new synthesis of N-acetoxy-N-acetyl-arylamines.

A new and simple synthesis is described for N-acetoxy-N-acetyl-derivatives of trans-4-aminostilbene, 2-aminofluorene and 2-aminophenanthrene using a Zn/Cu-couple for the reduction of the nitro-aromatics. This method produces good yields and should also be applicable for other N-aryl-compounds. It can also be used for the reduction of nitro-aromatics to the respective arylamines and arylamides.

Copper↗
PubMed1983

[Chondrocyte proliferation in joint cartilages in beginning arthrosis--experimental studies].

The cellular reaction of the articular cartilage in the beginning of the arthrosis has not been investigated very often up to now. An arthrosis model of little progression was used for this investigation by operative production of a valgus position of the proximal tibia at an angle of 30 degrees in the knee-joint of adult rabbits (in connection with Reimann, 1973). Proliferative processes of the chondrocytes are in the foreground with the beginning of arthrosis. This could be observed by means of histological and autoradiographical investigations with 3H-thymidine. The mode of the cell division is discussed. Mitotic divisions after modulation of the chondrocytes in a chondroblastic phase are probable.

Animals↗