General Enzymology of the Lung

Mustafa, Mohammad G.

doi:10.1007/978-3-642-69521-6_13

Cited by 7 publications

(2 citation statements)

References 275 publications

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“…The roles of bioactivation in toxicity, conversion from proximate to ultimate toxins, and pathways of detoxification and of protection are well known for many chemicals, including carcinogens (2,3). And for many of the same agents, information is available on the biochemical changes they produce in lung tissue or in isolated lung cells (4 will not necessarily always produce the same ultimate tissue lesions in the lungs of different species. On the other hand, similar lesions are often the result of initially quite different mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Responses of the Lung to Toxic Injury

Witschi¹

1990

Environmental Health Perspectives

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Section: Introductionmentioning

confidence: 99%

Responses of the Lung to Toxic Injury

Witschi¹

1990

Environmental Health Perspectives

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Section: Introductionmentioning

confidence: 99%

Responses of the lung to toxic injury.

Witschi

1990

Environ Health Perspect

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Analysis of toxic lung damage may focus on the offending agent and define patterns of bioactivation and interactions with the target tissues. It may also focus on a study of the biological response. While it was originally thought that cell proliferation, particularly Type II epithelial cell proliferation following lung injury, was a common event, it now has become obvious that on occasion proliferation occurs only late after the initial lung damage. Also Type II cell proliferation can occur in the absence of alveolar Type I cell damage. Delayed reepithelialization of the alveolar surface may lead to pulmonary fibrosis. Toxicological interactions often can be best recognized and defined by the extensive lesions that result from concomitant or sequential exposure to such toxic agents as ozone and acidic aerosols or anticancer drugs and oxygen. A correlation of cell proliferation and tumor development in mouse lung has shown that target cell hyperplasia is not a necessary prerequisite for enhanced tumor development. On the other hand, oxygen-induced proliferation of the neuroendocrine cell population results in the short-term development of neuroendocrine lung cell cancer in hamsters. While it is possible to draw some conclusions from an analysis of the lung response to toxic injury, predictions made from such knowledge are sometimes, but not necessarily always, correct.

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Comparative kinetic studies on aflatoxin B₁ binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally

Biswas

Raj

Allameh

et al. 1993

Teratog Carcinog Mutagen

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Several epidemiological studies have discussed the outcome of inhalation of airborne aflatoxins by humans. Metabolism of aflatoxin B1 (AFB1) by lung parenchyma leading to DNA binding is reported here. The tissue distribution pattern of [3H]AFB1 radioactivity revealed the lungs to be the second most important organ after the liver to retain a considerable amount of the radioactivity (66%). The lung indicated a selective activation of AFB1 as it showed only 7.7% binding of [3H]AFB1 to pulmonary DNA. Rats and hamsters were dosed with [3H]AFB1 (2 microCi containing 40 micrograms AFB1/100 g body wt.) intratracheally (i.t.) and sacrificed at different intervals after toxin treatment. Peak binding occurred at 0.5, 1, and 2 h in case of hamster lung, rat lung, and alveolar macrophages of both the species, respectively. At the end of 24 h, the relative AFB1-DNA binding (percentage of peak binding) in hamster lung was 72% while that in rat was 24%. The relative binding in rat lung alveolar macrophages (AMs) was generally higher than that of the hamster. AFB1 binding to hepatic DNA of both the species approached the peak at 1 h after the toxin administration i.t. Under these conditions, binding of AFB1 (or its metabolites translocated to liver) to hepatic DNA of both the species progressively diminished with time in contrast to lung, as revealed by the relative binding values at 12 h for rat and hamster lung, which were 48 and 67%, respectively, while for the rat and hamster liver they were 28 and 24%, respectively. Binding of i.t. administered [3H]AFB1 to rat liver DNA is only marginally higher than that observed with hamster liver, in contrast to the wide difference observed in animals receiving AFB1 intraperitoneally. These results highlight the persistence of AFB1 binding to pulmonary DNA, and the extent of translocated AFB1 binding to hepatic DNA presents an interesting difference from that observed when the toxin was administered through a gastrointestinal route. It is worth concluding that AMs unlike many other xenobiotics, possess specific mixed function oxidase activity to epoxidize AFB1.

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General Enzymology of the Lung

Cited by 7 publications

References 275 publications

Responses of the Lung to Toxic Injury

Responses of the Lung to Toxic Injury

Responses of the lung to toxic injury.

Comparative kinetic studies on aflatoxin B₁ binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally

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General Enzymology of the Lung

Cited by 7 publications

References 275 publications

Responses of the Lung to Toxic Injury

Responses of the Lung to Toxic Injury

Responses of the lung to toxic injury.

Comparative kinetic studies on aflatoxin B1 binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally

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Comparative kinetic studies on aflatoxin B₁ binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally