Isolated perfused rabbit lung: a critical appraisal.

Niemeier, Richard W.

doi:10.1289/ehp.761667

Cited by 11 publications

(2 citation statements)

References 8 publications

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“…pretreatments of the rabbits were based on proportional doses used in hamsters (Saffiotti et al, 1972), and the ip doses to the whole animal with BaP, 3MC, and phenobarbital were based on prior standard dose levels used in enzyme induction studies (Grover et al, 1972;Lake et al, 1973). The equipment, perfusion system, preparation of the lung, and the method for intratracheal pretreatment are described elsewhere (Niemeier, 1976;Niemeier and Bingham, 1972;Warshawsky et al, 1980.…”

Section: Lung Perfusionmentioning

confidence: 99%

“…The isolated perfused rabbit lung (IPL) preparation reflects the biochemical events that occur in vivo in the organ and therefore is an excellent preparation for investigating pulmonary metabolism of foreign compounds (Mehendale et al, 1981;Niemeier, 1976;Roth, 1979;Smith et al, 1980) adsorbed onto airborne particulate matter . Comparative metabolism of compounds of varying physical states in lung tissue of different cell types (Lubawy and Perrier, 1980;Warshawsky etal., 1981Warshawsky etal., , 1983Warshawsky and Myers, 1981) can be studied in the whole lung preparation.…”

Section: Introductionmentioning

confidence: 99%

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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: Lung Perfusionmentioning

confidence: 99%

Section: Introductionmentioning

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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Mutagenicity of benzo(a)pyrene metabolites generated on the isolated perfused lung following particulate exposure

Schoeny

Warshawsky

1983

Teratog. Carcinog. Mutagen.

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The isolated perfused rabbit lung (IPL) is being used to study the effects of particulate exposure on the pulmonary metabolism of benzo(a)pyrene (BaP). Pasturealla-free New Zealand white rabbits were treated intraperitoneally with BaP prior to kill. The isolated lungs were then administered either 14C-labeled BaP alone or BaP plus Fe2O3 or fly ash by intratracheal injection. Rates of appearance of BaP metabolites in the perfusing blood were determined. The extent of metabolism, distribution of metabolites, and types of metabolites produced were quantified for various lung tissue types by high-performance liquid chromatography and liquid scintillation spectrometry. Procedures were developed to apply the Salmonella/microsome test in the assay of mutagenicity of lung tissue and blood extracts as an indicator of their biologic activity. With few exceptions, blood extracts from IPL receiving BaP only were not mutagenic. Lung, trachea-bronchi, and macrophage extracts, by contrast, were mutagenic. A part of this activity could be attributed to BaP metabolites rather than to parent compound remaining in extracts. When lungs were exposed to Fe2O3 or to fly ash, only macrophage extracts were consistently mutagenic. This activity was due to significant amounts of unmetabolized BaP.

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Use of isolated perfused lung in determining pulmonary disposition and potential toxicological significance of inhaled environmental pollutants

Mehendale

1982

Enviro Toxic and Chemistry

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Recent interest in the investigation of the effect of environmental pollutants on the nonrespiratory and respiratory functions of the lung has stimulated the refinement and application of the technique of perfusing isolated intact lung preparations from suitable experimental animals in toxicological and biochemical studies. Available techniques include perfusion with whole blood or constituted perfusion media via pulmonary artery while maintaining ventilation with alternating negative or positive pressure. Viable, ventilating lung preparations can be maintained for 3 h. Such preparations have been employed for studies of uptake, metabolism and disposition of intratracheally or vascularly administered endogenous or exogenous chemicals. Recent development in unilateral or split‐lung perfusion preparations will undoubtedly further enhance the application of these techniques in the study of the interactions of endogenous and exogenous substances in the lung tissue. Isolated, perfused split‐lung preparations are particularly suited to investigate early toxic effects of inhaled pollutants in an attempt to gain insight into underlying mechanisms that lead to lung injury. Areas in which intact perfused lungs have been employed extensively with notable success include uptake, metabolism and disposition of toxic chemicals. These preparations have been used to study the effects of gases such as SO2, NO2, O3 and CO on lung metabolism. Perfused lung preparations have been particularly useful in demonstrating pulmonary activation of toxic chemicals and in the demonstration of specific effects on the lung after chronic administration of chemicals. Areas which have not been actively investigated include the uptake and disposition of gases or vapors, effects of toxic chemicals on respiratory and nonrespiratory functions of the lung and alteration in the hemodynamics of the pulmonary circulation in the presence of interacting chemical or physical agents. It should be technically feasible to adapt the perfused lung preparations for such investigations, and interest in this area will continue.

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Isolated perfused rabbit lung: a critical appraisal.

Cited by 11 publications

References 8 publications

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

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

Mutagenicity of benzo(a)pyrene metabolites generated on the isolated perfused lung following particulate exposure

Use of isolated perfused lung in determining pulmonary disposition and potential toxicological significance of inhaled environmental pollutants

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