Search results for "Chlorin"

Interspecies differences in cancer susceptibility and toxicity.

1999

One of the most complex challenges to the toxicologist represents extrapolation from laboratory animals to humans. In this article, we review interspecies differences in metabolism and toxicity of heterocyclic amines, aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and related compounds, endocrine disrupters, polycyclic aromatic hydrocarbons, tamoxifen, and digitoxin. As far as possible, extrapolations to human toxicity and carcinogenicity are performed. Humans may be more susceptible to the carcinogenic effect of heterocyclic amines than monkeys, rats, and mice. Especially, individuals with high CYP1A2 and 3A4 activities and the rapid acetylator phenotype may be expected to have …

DNA binding, adduct characterisation and metabolic activation of aflatoxin B1 catalysed by isolated rat liver parenchymal, Kupffer and endothelial ce…

1991

In vitro studies with rat liver parenchymal, Kupffer and endothelial cells isolated from male Sprague-Dawley rats were undertaken to investigate cell-specific bioactivation of aflatoxin B1, DNA binding and adduct formation. In the mutagenicity studies, using homogenates of all three separated liver cell populations (co-incubated with NADP+ and glucose-6-phosphate as cofactors for the cytochrome P-450 monooxygenase system) parenchymal, Kupffer and endothelial cells were able to activate aflatoxin B1 to a metabolite mutagenic to Salmonella typhimurium TA 98. In the case of nonparenchymal cells (i.e. Kupffer and endothelial cells) 10-fold higher concentrations of aflatoxin B1 had to be used to…

Polychlorinated diphenyl ethers, dibenzo-p-dioxins, dibenzofurans and biphenyls in seals and sediment from the Gulf of Finland.

1997

Polychlorinated diphenyl ethers (PCDEs), 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in seals from the Gulf of Finland and in sediments from the Gulf of Finland and near Gotland. The sediments included one surface core from both sampling sites. The seal material consisted of 14 ringed seals and 6 grey seals that all were found dead and examined for pathology. The main aims were to scrutinize levels and patterns of PCDEs for the first time in seals from the Baltic Sea and to estimate whether chlorinated compounds mentioned have an influence on an exceptional high mortality that occurred among ring…

Large differences in metabolic activation and inactivation of chemically closely related compounds: effects of pure enzymes and enzyme induction on t…

1981

Xenobiotic metabolizing enzymes of rat liver nonparenchymal cells.

1986

Abstract The nonparenchymal cells (NPC) of the liver are primarily located along the sinusoids and therefore are the first cells to encounter blood-borne xenobiotics. To study the possible role of the NPC in the metabolism of xenobiotics, populations of NPC and parenchymal cells (PC) were prepared from rats and various xenobiotic metabolizing enzyme activities investigated. The specific activity of every enzyme studied (ethoxyresorufin deethylase, benzphetamine demethylase, glutathione transferase, UDP glucuronosyltransferase, and microsomal epoxide hydrolase) was 12 to 1000% higher in the PC than in the NPC populations and the patterns of activities between the two populations were remarka…

THE DISTRIBUTION OF UDP-GLUCURONOSYLTRANSFERASES IN RAT-LIVER PARENCHYMAL AND NONPARENCHYMAL CELLS

1992

Activities for the glucuronidation of 1-naphthol, morphine and bilirubin as well as for the sulfation of 2-naphthol have been determined in homogenates of parenchymal, Kupffer and endothelial cells isolated from livers of untreated and Aroclor 1254-pretreated rats. In addition, Western blot analyses using different polyclonal antibodies against UDP-glucuronosyltransferases (UDP-GTs) were performed with similar preparations. All enzymes under investigation were expressed at high levels in liver parenchymal cells. The constitutive expression and inducibility of UDP-GT isozyme(s) for 1-naphthol glucuronidation was also clearly demonstrated in Kupffer and endothelial cells. Furthermore, the pre…

A comparative study of drug-metabolizing enzymes present in isolated rat liver parenchymal, Kupffer and endothelial cells

1987

Metabolic Activation of the (+)-S,S- and (−)-R,R-Enantiomers of trans-11,12-Dihydroxy-11,12-dihydrodibenzo[a,l]pyrene:  Stereoselectivity, DNA Adduct…

1997

Polycyclic aromatic hydrocarbons require metabolic activation in order to exert their biological activity initiated by DNA binding. The metabolic pathway leading to bay or fjord region dihydrodiol epoxides as ultimate mutagenic and/or carcinogenic metabolites is thought to play a dominant role. For dibenzo[a,l]pyrene, considered as the most potent carcinogenic polycyclic aromatic hydrocarbon, the formation of the fjord region syn- and/or anti-11,12-dihydrodiol 13,-14-epoxide (DB[a,l]PDE) diastereomers has been found to be the principal metabolic activation pathway in cell cultures leading to DNA adducts. In order to further elucidate the stereoselectivity involved in this activation pathway…

Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices

1996

1. The effect of some xenobiotics on levels of selected cytochrome P450 (CYP) isoenzymes determined by Western immunoblotting and associated enzyme activities has been studied in 72-h cultured rat and human precision-cut liver slices. 2. In cultured rat liver slices, 0.5 mM sodium phenobarbitone (PB), 25 microM beta-naphthoflavone (BNF), and 20 micrograms/ml Aroclor 1254 (ARO) induced mixed-function oxidase enzyme activities. Western immunoblotting of liver slice microsomes was performed with antibodies to rat CYP1A2, 2B1/2 and 3A. Compared with 72-h control (dimethyl sulphoxide only treated) rat liver slice microsomes, PB induced CYP2B1/2 and 3A, BNF induced CYP1A2, and ARO induced CYP1A2,…

Long-term effects of commercial and congeneric polychlorinated biphenyls on ethane production and malondialdehyde levels, indicators of in vivo lipid…

1988

Ethane exhalation was increased in male Sprague-Dawley rats following a single intraperitoneal (IP) injection of Aroclor 1254 (500 mg/kg). In the first 2 weeks following Aroclor 1254 treatment, the increase in ethane exhalation was due to an inhibition of metabolism of endogenous ethane rather than to an increase in ethane production. In weeks 3 and 4 following Aroclor 1254 administration, metabolic clearance of ethane returned to and exceeded control levels, while ethane production increased to approximately twice the control rates (day 30). The HPLC determination of in situ hepatic malondialdehyde levels revealed a 2-fold increase in malondialdehyde content on day 30 following the Aroclor…