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Biomedical subjects

H M Bolt

Publications and source records attributed to H M Bolt.

At least 199 records · Page 11Linked to original sources
PubMed1980

[The enterohepatic circulation of estradiol and ethinylestradiol in the rat].

After intraduodenal administration of 6,7-3H-estradiol to rats about 56% of the radioactive dose is excreted in the bile within 4.5 h. The bulk of this radioactivity is confined to glucuronide conjugates. By using different methods it is shown that 12-16% of the administered estradiol dose is excreted in bile as glucuronides of estrone and estradiol. Similarly, after i.v. administration of 6,7-3H-ethinylestradiol 12% of this dose appears in bile of rats as ethinylestradiolgucuronide. Thes conjugates of the biologically active estrogens (estrone, estradiol, ethinylestradiol), upon removal of the glucuronic acid moiety by action of gut bacterial enzymes, may make available the active estrogenic compounds to the enterohepatic circulation. Therefore, enterohepatic circulation of estrogens may be of some biological importance in the rat.

Animals↗
PubMed1980

Metabolic activation of vinyl chloride and vinyl bromide by isolated hepatocytes and hepatic sinusoidal cells.

The formation of liver sinusoidal cell tumors after exposure to vinyl chloride led to a survey of hepatocytes and sinusoidal cells isolated from rat liver as to their ability to metabolically activate vinyl chloride and vinyl bromide. It is shown that metabolism of these vinyl halides to reactive metabolites is confined primarily to hepatocytes. This favours the theory that in the liver reactive metabolites of vinyl chloride leave the hepatocytes to act on hepatic sinusoidal cells.

Animals↗
PubMed1979

[The animal experiment in toxicology. Current situation and further development].

In view of recent public reproaches against medical animal experimentation this article describes the present status of animal experimentation in the field of toxicology. Possible perspectives and the limitations of "alternative" methods are reviewed. Toxicological methods which are based on cell culture and metabolic in vitro-systems, as well as "short-term-tests" for mutagenicity and/or carcinogenicity are invaluable for screening purposes. However, a risk assessment, i.e., evaluation of hazard of chemical compounds to man, must be based on animal experiments. Further efforts must be directed towards improvement of extrapolation of toxicological results from one species to the other.

Animals↗
PubMed1979

Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver.

[1,2-14C] Vinyl chloride and [1,2-14C] trichloroethylene were incubated with rat liver microsomes, NADPH and RNA (from yeast). Whereas trichloroethylene metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than vinyl chloride metabolites, irreversible binding to RNA was lower for trichloroethylene metabolites. Hydrolysis of the RNA which was reisolated from microsomal incubations with 14C-vinyl chloride or 14C-trichloroethylene and separation of the nucleosides showed different alkylation products arising from vinyl chloride and from trichloroethylene, characteristic for vinyl chloride being formation of 1,N6-ethenoadenosine and 3,N4-enthenocytidine. The different reactivities of metabolites of vinyl chloride and of trichloroethylene prompted a comparison of the oncogenic effects of both compounds against the rat liver cell. Newborn rats were exposed for 10 weeks to 2000 ppm vinyl chloride or trichloroethylene (8 h/day; 5 days/week). After this period livers of the animals were stained for nucleoside-5-triphosphatase. Whereas the vinyl chloride exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy, no such changes were induced by trichloroethylene exposure. The data therefore suggest differences between the hepatocarcinogenic activity of vinyl chloride and possible effects of trichloroethylene on the liver.

Adenosine↗
PubMed1979

Alkylation of RNA by vinyl bromide metabolites in vitro and in vivo.

[1,2-14C]Vinyl bromide was incubated with rat liver microsomes, NADPH, and polyadenylic acid, polycytidylic acid, or RNA, respectively. Part of the adenosine moieties in RNA or in polyadenylic acid were alkylated and labelled 1,N6-ethenoadenosine structures were formed. Part of the cytidine moieties were converted into 3,N4-ethenocytidine. In addition, a further unidentified cytidine alkylation product was observed which was not seen in experiments using [1,2-14C]vinyl chloride. When rats were exposed to [1,2-14C]vinyl bromide, radioactive ethenoadenosine and ethenocytidine were present in hydrolysates of liver RNA. A further alkylation product was observed in the RNA hydrolysates which did not occur in experiments using [14C]vinyl chloride. The data show that vinyl bromide metabolites alkylate nucleic acids; although in general in this respect vinyl bromide and vinyl chloride behave similarly, some differences are observed in the alkylation behaviour of both compounds.

Alkylation↗
PubMed1978

Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolities in vitro and in vivo.

Rats were exposed to [1,2-14C] vinyl chloride. Liver RNA was isolated, hydrolyzed, and the nucleosides separated on Aminex-A-6. Besides the physiological bases and 1,N6-ethenoadenosine, radioactivity was also incorporated into 3,N4-ethenocytidine. Radioactive 3,N4-ethenocytidine moieties were also formed on incubation of polycytidylic acid with rat liver microsomes, NADPH and [14C] vinyl chloride. These alkylation mechanisms are consistent with the mutagenic and cancerogenic properties of vinyl chloride.

Animals↗