Pulmonary Cytochromes P-450 from Rabbits Treated with Phenobarbital

Ueng, Tzuu‐Huei; Alvares, Alvito P.

doi:10.1159/000138096

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…The changes in the metabolic profile were slight. Both 3MC and BaP intraperitoneal pretreatments to the whole animal in comparison with corn oil pretreatments increased the metabolite production (Lubawy and Isaac, 1980b;Smith et al, 1978;Ueng and Alvares, 1982), as evidenced by the total rate of appearance of metabolites of BaP in the blood (836 ± 343 and 1718 ± 287 versus 466 ± 94 ng/g lung'h, ± SE). The BaP pretreatment induced BaP metabolism in lung to a greater extent (p -0.01) than 3MC pretreatment.…”

Section: Influence Of Pretreatment Of Enzyme Inducers On the Metabolimentioning

confidence: 99%

The effects of a cocarcinogen, ferric oxide, on the metabolism of benzo[a]pyrene in the isolated perfused lung

Warshawsky

Bingham

Niemeier

1984

Journal of Toxicology and Environmental Health

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An isolated perfused New Zealand rabbit lung preparation was used to investigate the effects of a cocarcinogen, ferric oxide (Fe2O3), on the metabolism of benzo[a]pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of human bronchiogenic carcinoma in occupational and urban settings. [14C]-BaP was administered intratracheally to an isolated perfused lung (IPL) preparation with and without Fe2O3 after intraperitoneal pretreatment of the whole animal with BaP or intratracheal pretreatment of the whole animal with Fe2O3 and/or BaP. BaP and its metabolites were isolated from serial blood samples up to 180 min after administration of [14C]BaP to the IPL. BaP and its metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by chromatographic techniques and liquid scintillation counting. Fe2O3 pretreatment to the whole animal or administration of Fe2O3 to the IPL altered BaP metabolism by the perfused lung. Fe2O3 pretreatment to the whole animal resulted in an increase in the total rate of appearance of metabolites of BaP in the blood (ng/g lung X h), while Fe2O3 administration to the IPL resulted in a decrease in the total rate of appearance of BaP metabolites in the blood and inhibited the effect of pretreatment. Administration of Fe2O3 with BaP to the IPL with or without Fe2O3 pretreatment to the whole animal, or BaP administration to the IPL preceded by Fe2O3 pretreatment to the whole animal, enhanced dihydrodiol formation and depressed formation of water-soluble metabolites. Since dihydrodiol formation is considered to be the active pathway of BaP metabolism, these data suggest that pulmonary exposure to a known cocarcinogen, Fe2O3, in the presence of BaP results in increased production of dihydrodiols of BaP, which may be further metabolized to the ultimate carcinogenic form(s) of BaP. Therefore, Fe2O3 can enhance the metabolic activation of BaP by the lung, as well as act as a carrier for penetration and retention of BaP in the lung.

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Section: Influence Of Pretreatment Of Enzyme Inducers On the Metabolimentioning

confidence: 99%

The effects of a cocarcinogen, ferric oxide, on the metabolism of benzo[a]pyrene in the isolated perfused lung

Warshawsky

Bingham

Niemeier

1984

Journal of Toxicology and Environmental Health

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“…The rate of N-demethylation of benzphetamine indicative of P450IIB (P450 nomenclature according to Nebert et al 1987) activity (Ueng and Alvares 1982;Thabrew and Ioannides 1984) was in both the lung and the liver preparations highest in the rabbit, followed by that of rats and mice (Table 5). The P450I activity was determined by two assays, the rates of O-deethylation of 7-ethoxyresorufin and of hydroxylation of benzo(a)pyrene (Nebert and Gelboin 1968;Phillipson et al 1984) (Table 5).…”

Section: Microsomal Monooxygenase Activitiesmentioning

confidence: 99%

Species differences in short term toxicity from inhalation exposure to bromobenzene

Dahl¹,

Becher²,

Aarstad

et al. 1990

Arch Toxicol

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Lung, liver and kidney injury were studied in mice, rats and rabbits 48 h after termination of a 4 h inhalation exposure to bromobenzene vapour (250-3400 ppm). Light and electron microscopy of lung tissue revealed injury to Clara cells and adjacent epithelium in mouse bronchioli (bromobenzene concentration 250 ppm and 1000 ppm) and to Clara cells of rat bronchi and bronchioli (1000 ppm bromobenzene) and of rabbit bronchi (2500 ppm and 3400 ppm). Histological and clinicochemical indices of liver damage were found in the same animals, whereas kidney toxicity was observed in mice (two out of ten showed tubular necrosis and elevated concentration of plasma urea) and rats (all had elevated plasma concentrations of creatinine) exposed to 1000 ppm bromobenzene. Inhalation exposure thus produced less kidney injury than expected from previous studies with equimolar doses given intraperitoneally. The mouse was the most severely affected species, followed by the rat, and lastly the rabbit. The animal susceptibility could not be ranked according to the rate of 14C-bromobenzene covalent binding in lung or liver, but it was inversely related to the rate of N-demethylation of benzphetamine (indicative of P450IIB activity) in both lung and liver microsomal preparations. Differences in a P450 mediated detoxification could therefore be of importance in species variability to bromobenzene injury.

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“…Arochlor 1254 has been reported to suppress a form of rabbit pulmonary P-450 (Ueng & Alvares 1981). In addition it was noted that phenobarbital and trans-stilbene oxide, agents which induced forms PB, and PB2 in the liver, caused suppression of hepatic MC, and MC2.…”

Section: MCmentioning

confidence: 99%