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. 1984 Apr;55:139–148. doi: 10.1289/ehp.8455139

The role of toxicological interactions in lung injury.

H P Witschi, P J Hakkinen
PMCID: PMC1568374  PMID: 6376096

Abstract

Interactions between two or more toxic agents can produce lung damage by chemical-chemical interactions, chemical-receptor interactions or by modification, by a first agent, of the cell and tissue response to a second agent. Interactions may occur by simultaneous exposure and if exposure to the two agents is separated in time. Chemical-chemical interactions have been mostly studied in the toxicology of air pollutants, where it was shown that the untoward effect of certain oxidants may be enhanced in the presence of other aerosols. Interactions at the receptor site have been found in isolated perfused lung experiments. Oxygen tolerance may be an example, when pre-exposure to one concentration of oxygen mitigates later exposure to 100% oxygen by modifying cellular and enzymatic composition of the lung. Damage of the alveolar zone by the antioxidant butylated hydroxytoluene (BHT) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents.

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Selected References

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  1. AMDUR M. O. The influence of aerosols upon the respiratory response of guinea pigs to sulfur dioxide. Am Ind Hyg Assoc Q. 1957 Jun;18(2):149–155. doi: 10.1080/00968205709343484. [DOI] [PubMed] [Google Scholar]
  2. Abe M., Nishidai T., Yukawa Y., Takahashi M., Ono K., Hiraoka M., Ri N. Studies on the radioprotective effects of superoxide dismutase in mice. Int J Radiat Oncol Biol Phys. 1981 Feb;7(2):205–209. doi: 10.1016/0360-3016(81)90438-7. [DOI] [PubMed] [Google Scholar]
  3. Adamson I. Y., Bowden D. H., Cote M. G., Witschi H. Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice. Lab Invest. 1977 Jan;36(1):26–32. [PubMed] [Google Scholar]
  4. Amdur M. O. Aerosols formed by oxidation of sulfur dioxide. Review of their toxicology. Arch Environ Health. 1971 Dec;23(6):459–468. doi: 10.1080/00039896.1971.10666036. [DOI] [PubMed] [Google Scholar]
  5. Amdur M. O., Underhill D. The effect of various aerosols on the response of guinea pigs to sulfur dioxide. Arch Environ Health. 1968 Apr;16(4):460–468. doi: 10.1080/00039896.1968.10665090. [DOI] [PubMed] [Google Scholar]
  6. Angevine L. S., Mehendale H. M. Effect of chlorphentermine on the pulmonary disposition of 5-hydroxytryptamine in the isolated perfused rabbit lung. Am Rev Respir Dis. 1980 Dec;122(6):891–898. doi: 10.1164/arrd.1980.122.6.891. [DOI] [PubMed] [Google Scholar]
  7. Autor A. P. Reduction of paraquat toxicity by superoxide dismutase. Life Sci. 1974 Apr 1;14(7):1309–1319. doi: 10.1016/0024-3205(74)90439-1. [DOI] [PubMed] [Google Scholar]
  8. Baldwin R. C., Pasi A., MacGregor J. T., Hine C. H. The rates kof radical formation from dipyridylium herbicides paraquat, diquat, and morfamquat in homogenates of rat lung, kidney, and liver: an inhibitory effect of carbon monoxide. Toxicol Appl Pharmacol. 1975 May;32(2):298–304. doi: 10.1016/0041-008x(75)90220-3. [DOI] [PubMed] [Google Scholar]
  9. Bedi J. F., Folinsbee L. J., Horvath S. M., Ebenstein R. S. Human exposure to sulfur dioxide and ozone: absence of a synergistic effect. Arch Environ Health. 1979 Jul-Aug;34(4):233–239. doi: 10.1080/00039896.1979.10667405. [DOI] [PubMed] [Google Scholar]
  10. Bell K. A., Linn W. S., Hazucha M., Hackney J. D., Bates D. V. Respiratory effects of exposure to ozone plus sulfur dioxide in Southern Californians and Eastern Canadians. Am Ind Hyg Assoc J. 1977 Dec;38(12):696–706. doi: 10.1080/0002889778507681. [DOI] [PubMed] [Google Scholar]
  11. Bilimoria M. H., Johnson J., Hogg J. C., Witschi H. P. Pulmonary aryl hydrocarbon hydroxylase: tobacco smoke-exposed guinea pigs. Toxicol Appl Pharmacol. 1977 Aug;41(2):433–440. doi: 10.1016/0041-008x(77)90044-8. [DOI] [PubMed] [Google Scholar]
  12. Block E. R. Potentiation of acute paraquat toxicity by vitamin E deficiency. Lung. 1979;156(3):195–203. doi: 10.1007/BF02714010. [DOI] [PubMed] [Google Scholar]
  13. Boyd M. R. Biochemical mechanisms in chemical-induced lung injury: roles of metabolic activation. Crit Rev Toxicol. 1980 Aug;7(2):103–176. doi: 10.3109/10408448009037487. [DOI] [PubMed] [Google Scholar]
  14. Boyd M. R., Burka L. T. In vivo studies on the relationship between target organ alkylation and the pulmonary toxicity of a chemically reactive metabolite of 4-ipomeanol. J Pharmacol Exp Ther. 1978 Dec;207(3):687–697. [PubMed] [Google Scholar]
  15. Boyd M. R., Burka L. T., Wilson B. J., Sastry B. V. Development of tolerance to the pulmonary toxin, 4-ipomeanol. Toxicology. 1981;19(2):85–100. doi: 10.1016/0300-483x(81)90091-3. [DOI] [PubMed] [Google Scholar]
  16. Boyd M. R., Catignani G. L., Sasame H. A., Mitchell J. R., Stiko A. W. Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen. Am Rev Respir Dis. 1979 Jul;120(1):93–99. doi: 10.1164/arrd.1979.120.1.93. [DOI] [PubMed] [Google Scholar]
  17. Boyd M. R., Neal R. A. Studies on the mechanism of toxicity and of development of tolerance to the pulmonary toxin, alpha-naphthylthiourea (ANTU). Drug Metab Dispos. 1976 Jul-Aug;4(4):314–322. [PubMed] [Google Scholar]
  18. Bus J. S., Gibson J. E. Postnatal toxicity of chronically administered paraquat in mice and interactions with oxygen and bromobenzene. Toxicol Appl Pharmacol. 1975 Sep;33(3):461–470. doi: 10.1016/0041-008x(75)90072-1. [DOI] [PubMed] [Google Scholar]
  19. CULLUMBINE H., PATTLE R. E. Toxicity of some atmospheric pollutants. Br Med J. 1956 Oct 20;2(4998):913–916. doi: 10.1136/bmj.2.4998.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Collis C. H., Wilson C. M., Jones J. M. Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose. Br J Cancer. 1980 Jun;41(6):901–907. doi: 10.1038/bjc.1980.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Conney A. H., Burns J. J. Metabolic interactions among environmental chemicals and drugs. Science. 1972 Nov 10;178(4061):576–586. doi: 10.1126/science.178.4061.576. [DOI] [PubMed] [Google Scholar]
  22. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  23. Cooper D. W., Underhill D. W., Ellenbecker M. J. A critique of the U.S. standard for industrial exposure to sodium hydroxide aerosols. Am Ind Hyg Assoc J. 1979 May;40(5):365–371. doi: 10.1080/15298667991429705. [DOI] [PubMed] [Google Scholar]
  24. Crapo J. D., Barry B. E., Foscue H. A., Shelburne J. Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am Rev Respir Dis. 1980 Jul;122(1):123–143. doi: 10.1164/arrd.1980.122.1.123. [DOI] [PubMed] [Google Scholar]
  25. Crapo J. D., DeLong D. M., Sjostrom K., Hasler G. R., Drew R. T. The failure of aerosolized superoxide dismutase to modify pulmonary oxygen toxicity. Am Rev Respir Dis. 1977 Jun;115(6):1027–1033. doi: 10.1164/arrd.1977.115.6.1027. [DOI] [PubMed] [Google Scholar]
  26. Crapo J. D., Marsh-Salin J., Ingram P., Pratt P. C. Tolerance and cross-tolerance using NO2 and O2 II. Pulmonary morphology and morphometry. J Appl Physiol Respir Environ Exerc Physiol. 1978 Mar;44(3):370–379. doi: 10.1152/jappl.1978.44.3.370. [DOI] [PubMed] [Google Scholar]
  27. Crapo J. D., McCord J. M. Oxygen-induced changes in pulmonary superoxide dismutase assayed by antibody titrations. Am J Physiol. 1976 Oct;231(4):1196–1203. doi: 10.1152/ajplegacy.1976.231.4.1196. [DOI] [PubMed] [Google Scholar]
  28. Crapo J. D., Sjostrom K., Drew R. T. Tolerance and cross-tolerance using NO2 and O2. I. Toxicology and biochemistry. J Appl Physiol Respir Environ Exerc Physiol. 1978 Mar;44(3):364–369. doi: 10.1152/jappl.1978.44.3.364. [DOI] [PubMed] [Google Scholar]
  29. Crapo J. D., Tierney D. F. Superoxide dismutase and pulmonary oxygen toxicity. Am J Physiol. 1974 Jun;226(6):1401–1407. doi: 10.1152/ajplegacy.1974.226.6.1401. [DOI] [PubMed] [Google Scholar]
  30. Deneke S. M., Bernstein S. P., Fanburg B. L. Enhancement by disulfiram (Antabuse) of toxic effects of 95 to 97% O2 on the rat lung. J Pharmacol Exp Ther. 1979 Mar;208(3):377–380. [PubMed] [Google Scholar]
  31. Einhorn L., Krause M., Hornback N., Furnas B. Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer. Cancer. 1976 May;37(5):2414–2416. doi: 10.1002/1097-0142(197605)37:5<2414::aid-cncr2820370533>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  32. Fairshter R. D., Dabir-Vaziri N., Smith W. R., Glauser F. L., Wilson A. F. Paraquat poisoning: an analytical toxicologic study of three cases. Toxicology. 1979 Mar-Apr;12(3):259–266. doi: 10.1016/0300-483x(79)90071-4. [DOI] [PubMed] [Google Scholar]
  33. Fairshter R. D., Rosen S. M., Smith W. R., Glauser F. L., McRae D. M., Wilson A. F. Paraquat poisoning: new aspects of therapy. Q J Med. 1976 Oct;45(180):551–565. [PubMed] [Google Scholar]
  34. Fisher A. B., Pietra G. G. Comparison of serotonin uptake from the alveolar and capillary spaces of isolated rat lung. Am Rev Respir Dis. 1981 Jan;123(1):74–78. doi: 10.1164/arrd.1981.123.1.74. [DOI] [PubMed] [Google Scholar]
  35. Fisher H. K., Clements J. A., Wright R. R. Enhancement of oxygen toxicity by the herbicide paraquat. Am Rev Respir Dis. 1973 Feb;107(2):246–252. doi: 10.1164/arrd.1973.107.2.246. [DOI] [PubMed] [Google Scholar]
  36. Frank L., Bucher J. R., Roberts R. J. Oxygen toxicity in neonatal and adult animals of various species. J Appl Physiol Respir Environ Exerc Physiol. 1978 Nov;45(5):699–704. doi: 10.1152/jappl.1978.45.5.699. [DOI] [PubMed] [Google Scholar]
  37. Frank L., Roberts R. J. Endotoxin protection against oxygen-induced acute and chronic lung injury. J Appl Physiol Respir Environ Exerc Physiol. 1979 Sep;47(3):577–581. doi: 10.1152/jappl.1979.47.3.577. [DOI] [PubMed] [Google Scholar]
  38. Frank L., Roberts R. J. Oxygen toxicity: protection of the lung by bacterial lipopolysaccharide (endotoxin). Toxicol Appl Pharmacol. 1979 Sep 30;50(3):371–380. doi: 10.1016/0041-008x(79)90389-2. [DOI] [PubMed] [Google Scholar]
  39. Frank L., Summerville J., Massaro D. Potection from oxygen toxicity with endotoxin. Role of the endogenous antioxidant enzymes of the lung. J Clin Invest. 1980 May;65(5):1104–1110. doi: 10.1172/JCI109763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Frank L., Wood D. L., Roberts R. J. Effect of diethyldithiocarbamate on oxygen toxicity and lung enzyme activity in immature and adult rats. Biochem Pharmacol. 1978 Jan 15;27(2):251–254. doi: 10.1016/0006-2952(78)90311-8. [DOI] [PubMed] [Google Scholar]
  41. Frank L., Yam J., Roberts R. J. The role of endotoxin in protection of adult rats from oxygen-induced lung toxicity. J Clin Invest. 1978 Feb;61(2):269–275. doi: 10.1172/JCI108936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Garner R. C., McLean A. E. Increased susceptibility to carbon tetrachloride poisoning in the rat after pretreatment with oral phenobarbitone. Biochem Pharmacol. 1969 Mar;18(3):645–650. doi: 10.1016/0006-2952(69)90089-6. [DOI] [PubMed] [Google Scholar]
  43. Gross N. J. Pulmonary effects of radiation therapy. Ann Intern Med. 1977 Jan;86(1):81–92. doi: 10.7326/0003-4819-86-1-81. [DOI] [PubMed] [Google Scholar]
  44. Hackney J. D., Evans M. J., Christie B. R. Effects of 60 and 80% oxygen on cell division in lung alveoli of squirrel monkeys. Aviat Space Environ Med. 1975 Jun;46(6):791–794. [PubMed] [Google Scholar]
  45. Hakkinen P. J., Whiteley J. W., Witschi H. R. Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice. Am Rev Respir Dis. 1982 Aug;126(2):281–285. doi: 10.1164/arrd.1982.126.2.281. [DOI] [PubMed] [Google Scholar]
  46. Hanzlik R. P., Stitt R., Traiger G. J. Toxic effects of methylcyclopentadienyl manganese tricarbonyl (MMT) in rats: role of metabolism. Toxicol Appl Pharmacol. 1980 Dec;56(3):353–360. doi: 10.1016/0041-008x(80)90068-x. [DOI] [PubMed] [Google Scholar]
  47. Haschek W. M., Meyer K. R., Ullrich R. L., Witschi H. P. Potentiation of chemically induced lung fibrosis by thorax irradiation. Int J Radiat Oncol Biol Phys. 1980 Apr;6(4):449–455. doi: 10.1016/0360-3016(80)90059-0. [DOI] [PubMed] [Google Scholar]
  48. Haschek W. M., Witschi H. Pulmonary fibrosis--a possible mechanism. Toxicol Appl Pharmacol. 1979 Dec;51(3):475–487. doi: 10.1016/0041-008x(79)90372-7. [DOI] [PubMed] [Google Scholar]
  49. Hazucha M., Bates D. V. Combined effect of ozone and sulphur dioxide on human pulmonary function. Nature. 1975 Sep 4;257(5521):50–51. doi: 10.1038/257050a0. [DOI] [PubMed] [Google Scholar]
  50. Hewitt W. R., Miyajima H., Côté M. G., Plaa G. L. Modification of haloalkane-induced hepatotoxicity by exogenous ketones and metabolic ketosis. Fed Proc. 1980 Nov;39(13):3118–3123. [PubMed] [Google Scholar]
  51. Hinderer R. K. Toxicity studies of methylcyclopentadienyl manganese tricarbonyl (MMT). Am Ind Hyg Assoc J. 1979 Feb;40(2):164–167. doi: 10.1080/15298667991429462. [DOI] [PubMed] [Google Scholar]
  52. Hirai K. I., Witschi H., Côté M. G. Electron microscopy of butylated hydroxytoluene-induced lung damage in mice. Exp Mol Pathol. 1977 Dec;27(3):295–308. doi: 10.1016/0014-4800(77)90002-8. [DOI] [PubMed] [Google Scholar]
  53. Hollinger M. A., Patwell S. W., Zuckerman J. E. Effect of endotoxin on thiourea induced pulmonary edema and pleural effusion. Res Commun Chem Pathol Pharmacol. 1981 Feb;31(2):217–222. [PubMed] [Google Scholar]
  54. Kehrer J. P., Haschek W. M., Witschi H. The influence of hyperoxia on the acute toxicity of paraquat and diquat. Drug Chem Toxicol. 1979;2(4):397–408. doi: 10.3109/01480547909016033. [DOI] [PubMed] [Google Scholar]
  55. Kehrer J. P., Witschi H. Effects of drug metabolism inhibitors on butylated hydroxytoluene-induced pulmonary toxicity in mice. Toxicol Appl Pharmacol. 1980 Apr;53(2):333–342. doi: 10.1016/0041-008x(80)90434-2. [DOI] [PubMed] [Google Scholar]
  56. Kehrer J. P., Witschi H. The effect of indomethacin, prednisolone and cis-4-hydroxyproline on pulmonary fibrosis produced by butylated hydroxytoluene and oxygen. Toxicology. 1981;20(4):281–288. doi: 10.1016/0300-483x(81)90035-4. [DOI] [PubMed] [Google Scholar]
  57. Kuo J. F., Brackett N. L., Stubbs J. W., Shoji M., Helfman D. M. Involvements of cyclic nucleotide systems in enlarged mice lungs produced by butylated hydroxytoluene. Biochem Pharmacol. 1978;27(12):1671–1675. doi: 10.1016/0006-2952(78)90177-6. [DOI] [PubMed] [Google Scholar]
  58. Larsen J. C., Tarding F. Stimulation of DNA synthesis in mouse and rat lung following administration and butylated hydroxytoluene. Arch Toxicol Suppl. 1978;(1):147–150. doi: 10.1007/978-3-642-66896-8_18. [DOI] [PubMed] [Google Scholar]
  59. Last J. A., Cross C. E. A new model for health effects of air pollutants: evidence for synergistic effects of mixtures of ozone and sulfuric acid aerosols on rat lungs. J Lab Clin Med. 1978 Feb;91(2):328–339. [PubMed] [Google Scholar]
  60. Last J. A., Jennings M. D., Schwartz L. W., Cross C. E. Glycoprotein secretion by tracheal explants cultured from rats exposed to ozone. Am Rev Respir Dis. 1977 Oct;116(4):695–703. doi: 10.1164/arrd.1977.116.4.695. [DOI] [PubMed] [Google Scholar]
  61. Le Mesurier S. M., Lykke A. W., Stewart B. W. Reduced yield of pulmonary surfactant: patterns of response following administration of chemicals to rats by inhalation. Toxicol Lett. 1980 Jan;5(1):89–93. doi: 10.1016/0378-4274(80)90153-8. [DOI] [PubMed] [Google Scholar]
  62. Linn W. S., Jones M. P., Bailey R. M., Kleinman M. T., Spier C. E., Fischer D. A., Hackney J. D. Respiratory effects of mixed nitrogen dioxide and sulfur dioxide in human volunteers under simulated ambient exposure conditions. Environ Res. 1980 Aug;22(2):431–438. doi: 10.1016/0013-9351(80)90155-3. [DOI] [PubMed] [Google Scholar]
  63. Lock E. A., Smith L. L., Rose M. S. Inhibition of paraquat accumulation in rat lung slices by a component of rat plasma and a variety of drugs and endogenous amines. Biochem Pharmacol. 1976 Aug 1;25(15):1769–1772. doi: 10.1016/0006-2952(76)90413-5. [DOI] [PubMed] [Google Scholar]
  64. MILLER E. C., MILLER J. A., BROWN R. R., MACDONALD J. C. On the protective action of certain polycyclic aromatic hydrocarbons against carcinogenesis by aminoazo dyes and 2-acetylaminofluorene. Cancer Res. 1958 May;18(4):469–477. [PubMed] [Google Scholar]
  65. Malanchuk M., Barkley N. P., Contner G. L. Interference of animal source ammonia with exposure chamber atmospheres containing acid particulate from automobile exhaust. J Environ Pathol Toxicol. 1980 Aug;4(1):265–276. [PubMed] [Google Scholar]
  66. Malkinson A. M. Prevention of butylated hydroxytoluene-induced lung damage in mice by cedar terpene administration. Toxicol Appl Pharmacol. 1979 Jul;49(3):551–560. doi: 10.1016/0041-008x(79)90457-5. [DOI] [PubMed] [Google Scholar]
  67. Marcotte J., Skelton F. S., Côté M. G., Witschi H. Induction of aryl hydrocarbon hydroxylase in rat lung by marijuana smoke. Toxicol Appl Pharmacol. 1975 Aug;33(2):231–245. doi: 10.1016/0041-008x(75)90090-3. [DOI] [PubMed] [Google Scholar]
  68. Marino A. A., Mitchell J. T. Lung damage in mice following intraperitoneal injection of butylated hydroxytoluene. Proc Soc Exp Biol Med. 1972 May;140(1):122–125. doi: 10.3181/00379727-140-36407. [DOI] [PubMed] [Google Scholar]
  69. Mason R. P., Holtzman J. L. The role of catalytic superoxide formation in the O2 inhibition of nitroreductase. Biochem Biophys Res Commun. 1975 Dec 15;67(4):1267–1274. doi: 10.1016/0006-291x(75)90163-1. [DOI] [PubMed] [Google Scholar]
  70. Mehendale H. M., Angevine L. S., Ohmiya Y. The isolated perfused lung--a critical evaluation. Toxicology. 1981;21(1):1–36. doi: 10.1016/0300-483x(81)90013-5. [DOI] [PubMed] [Google Scholar]
  71. Mielke H., Seiler K. U., Stumpf U., Wassermann O. Uber eine Beziehung zwischen dem Serotoninstoffwechsel und der pulmonalen Hypertonie bei Ratten nach Gabe verschiedener Anorektika. Z Kardiol. 1973 Dec;62(12):1090–1098. [PubMed] [Google Scholar]
  72. Mitchell J. R., Jollow D. J., Gillette J. R., Brodie B. B. Drug metabolism as a cause of drug toxicity. Drug Metab Dispos. 1973 Jan-Feb;1(1):418–423. [PubMed] [Google Scholar]
  73. Montgomery M. R. Interaction of paraquat with the pulmonary microsomal fatty acid desaturase system. Toxicol Appl Pharmacol. 1976 Jun;36(3):543–554. doi: 10.1016/0041-008x(76)90233-7. [DOI] [PubMed] [Google Scholar]
  74. Mustafa M. G., Tierney D. F. Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity. Am Rev Respir Dis. 1978 Dec;118(6):1061–1090. doi: 10.1164/arrd.1978.118.6.1061. [DOI] [PubMed] [Google Scholar]
  75. Omaye S. T., Reddy K. A., Cross C. E. Effect of butylated hydroxytoluene and other antioxidants on mouse lung metabolism. J Toxicol Environ Health. 1977 Dec;3(5-6):829–836. doi: 10.1080/15287397709529617. [DOI] [PubMed] [Google Scholar]
  76. Petkau A., Chelack W. S., Pleskach S. D. Letter: Protection of post-irradiated mice by superoxide dismutase. Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Mar;29(3):297–299. doi: 10.1080/09553007614550341. [DOI] [PubMed] [Google Scholar]
  77. Petkau A., Chelack W. S., Pleskach S. D., Meeker B. E., Brady C. M. Radioprotection of mice by superoxide dismutase. Biochem Biophys Res Commun. 1975 Aug 4;65(3):886–893. doi: 10.1016/s0006-291x(75)80468-2. [DOI] [PubMed] [Google Scholar]
  78. Phalen R. F., Kenoyer J. L., Crocker T. T., McClure T. R. Effects of sulfate aerosols in combination with ozone on elimination of tracer particles inhaled by rats. J Toxicol Environ Health. 1980 Jul;6(4):797–810. doi: 10.1080/15287398009529898. [DOI] [PubMed] [Google Scholar]
  79. Phillips T. L., Fu K. K. The interaction of drug and radiation effects on normal tissues. Int J Radiat Oncol Biol Phys. 1978 Jan-Feb;4(1-2):59–64. doi: 10.1016/0360-3016(78)90116-5. [DOI] [PubMed] [Google Scholar]
  80. Proctor D. F. Oronasal breathing and studies of effects of air pollutants on the lungs. Am Rev Respir Dis. 1981 Feb;123(2):242–243. doi: 10.1164/arrd.1981.123.2.242a. [DOI] [PubMed] [Google Scholar]
  81. Rechnagel R. O., Glende E. A., Jr Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. CRC Crit Rev Toxicol. 1973 Nov;2(3):263–297. doi: 10.3109/10408447309082019. [DOI] [PubMed] [Google Scholar]
  82. Reid W. D., Ilett K. F., Glick J. M., Krishna G. Metabolism and binding of aromatic hydrocarbons in the lung. Relationship to experimental bronchiolar necrosis. Am Rev Respir Dis. 1973 Apr;107(4):539–551. doi: 10.1164/arrd.1973.107.4.539. [DOI] [PubMed] [Google Scholar]
  83. Rose M. S., Smith L. L., Wyatt I. Evidence for energy-dependent accumulation of paraquat into rat lung. Nature. 1974 Nov 22;252(5481):314–315. doi: 10.1038/252314b0. [DOI] [PubMed] [Google Scholar]
  84. STOKINGER H. E. Toxicologic interactions of mixtures of air pollutants. Review of recent developments. Int J Air Pollut. 1960 Jun;2:313–326. [PubMed] [Google Scholar]
  85. Saccone G. T., Pariza M. W. Effects of dietary butylated hydroxytoluene and phenobarbital on the activities of ornithine decarboxylase and thymidine kinase in rat liver and lung. Cancer Lett. 1978 Sep;5(3):145–152. doi: 10.1016/s0304-3835(78)80031-7. [DOI] [PubMed] [Google Scholar]
  86. Saheb W., Witschi H. Lung growth in mice after a single dose of butylated hydroxytoluene. Toxicol Appl Pharmacol. 1975 Aug;33(2):309–319. doi: 10.1016/0041-008x(75)90097-6. [DOI] [PubMed] [Google Scholar]
  87. Sasame H. A., Boyd M. R. Superoxide and hydrogen peroxide production and NADPH oxidation stimulated by nitrofurantoin in lung microsomes: possible implications for toxicity. Life Sci. 1979 Mar 19;24(12):1091–1096. doi: 10.1016/0024-3205(79)90042-0. [DOI] [PubMed] [Google Scholar]
  88. Sheppard D., Wong W. S., Uehara C. F., Nadel J. A., Boushey H. A. Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Am Rev Respir Dis. 1980 Dec;122(6):873–878. doi: 10.1164/arrd.1980.122.6.873. [DOI] [PubMed] [Google Scholar]
  89. Smith L. J., Brody J. S. Influence of methylprednisolone on mouse alveolar type 2 cell response to acute lung injury. Am Rev Respir Dis. 1981 Apr;123(4 Pt 1):459–464. doi: 10.1164/arrd.1981.123.4.459. [DOI] [PubMed] [Google Scholar]
  90. Steel G. G., Adams K., Peckham M. J. Lung damage in C57B1 mice following thoracic irradiation: enhancement by chemotherapy. Br J Radiol. 1979 Sep;52(621):741–747. doi: 10.1259/0007-1285-52-621-741. [DOI] [PubMed] [Google Scholar]
  91. Stevens J. B., Autor A. P. Proposed mechanism for neonatal rat tolerance to normobaric hyperoxia. Fed Proc. 1980 Nov;39(13):3138–3143. [PubMed] [Google Scholar]
  92. Vesell E. S. Induction of drug-metabolizing enzymes in liver microsomes of mice and rats by softwood bedding. Science. 1967 Sep 1;157(3792):1057–1058. doi: 10.1126/science.157.3792.1057. [DOI] [PubMed] [Google Scholar]
  93. Välimäki M., Juva K., Rantanen J., Ekfors T., Niinikoski J. Collagen metabolism in rat lungs during chronic intermittent exposure to oxygen. Aviat Space Environ Med. 1975 May;46(5):684–690. [PubMed] [Google Scholar]
  94. Wasserman B., Block E. R. Prevention of acute paraquat toxicity in rats by superoxide dismutase. Aviat Space Environ Med. 1978 Jun;49(6):805–809. [PubMed] [Google Scholar]
  95. Wattenberg L. W. Inhibition of carcinogenic and toxic effects of polycyclic hydrocarbons by phenolic antioxidants and ethoxyquin. J Natl Cancer Inst. 1972 May;48(5):1425–1430. [PubMed] [Google Scholar]
  96. Witschi H. R., Haschek W. M., Klein-Szanto A. J., Hakkinen P. J. Potentiation of diffuse lung damage by oxygen: determining variables. Am Rev Respir Dis. 1981 Jan;123(1):98–103. doi: 10.1164/arrd.1981.123.1.98. [DOI] [PubMed] [Google Scholar]
  97. Witschi H., Côte M. G. Primary pulmonary responses to toxic agents. CRC Crit Rev Toxicol. 1977 May;5(1):23–66. doi: 10.3109/10408447709101341. [DOI] [PubMed] [Google Scholar]
  98. Witschi H., Cöté M. G. Inhibition of butylated hydroxytoluene-induced mouse lung cell division by oxygen: time-effect and dose-effect relationships. Chem Biol Interact. 1977 Dec;19(3):279–289. doi: 10.1016/0009-2797(77)90051-5. [DOI] [PubMed] [Google Scholar]
  99. Witschi H., Kacew S., Hirai K. I., Côté M. G. In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung. Chem Biol Interact. 1977 Nov;19(2):143–160. doi: 10.1016/0009-2797(77)90027-8. [DOI] [PubMed] [Google Scholar]
  100. Witschi H., Kacew S., Tsang B. K., Williamson D. Biochemical paramters of BHT-induced cell growth in mouse lung. Chem Biol Interact. 1976 Jan;12(1):29–40. doi: 10.1016/0009-2797(76)90064-8. [DOI] [PubMed] [Google Scholar]
  101. Witschi H., Lock S. Toxicity of butylated hydroxytoluene in mouse following oral administration. Toxicology. 1978 Feb;9(1-2):137–146. doi: 10.1016/0300-483x(78)90038-0. [DOI] [PubMed] [Google Scholar]
  102. Yam J., Frank L., Roberts R. J. Oxygen toxicity: comparison of lung biochemical responses in neonatal and adult rats. Pediatr Res. 1978 Feb;12(2):115–119. doi: 10.1203/00006450-197802000-00010. [DOI] [PubMed] [Google Scholar]

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