Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1993 Mar;99:249–252. doi: 10.1289/ehp.9399249

Pulmonary alveolar macrophages in molecular epidemiology and chemoprevention of cancer.

S De Flora 1, A Izzotti 1, F D'Agostini 1, G A Rossi 1, R M Balansky 1
PMCID: PMC1567068  PMID: 8319635

Abstract

In addition to possessing an extraordinary sweeping activity, pulmonary alveolar macrophages (PAM) are equipped with the biochemical mechanisms involved in the metabolism of carcinogens, which were found to be inducible in humans by cigarette smoke. Moreover, several defense processes were stimulated in rat PAM after in vivo administration of the anticarcinogen N-acetylcysteine (NAC). Benzo[a]pyrene diol epoxide (BPDE)-DNA adducts, as revealed by synchronous fluorescence spectrophotometry, were selectively detected in PAM of smokers and persisted up to 6 months. The amount of adducts was significantly correlated with the number of currently smoked cigarettes but not with the cigarettes smoked in a lifetime (pack-years). Nevertheless, deviations from the regression line pointed out the role of interindividual variability factors in adduct formation. Probably due to the low mitotic rate of PAM in the respiratory lumen, the frequency of micronuclei was not enhanced in smokers. However, parallel assays in rats showed that micronuclei can be enhanced after massive intratracheal administration of benzo[a]pyrene or whole-body exposure to high amounts of mainstream cigarette smoke, which also induced BPDE-DNA adducts in lung cells and other organs, including the heart. All these adverse effects were markedly inhibited by the oral administration of NAC, which provides the premise and rationale for a future study on the protective effects of oral NAC in heavy smokers.

Full text

PDF
249

Images in this article

250FIGURE 1.
on p.250
250FIGURE 1.
on p.250

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balansky R. M., Blagoeva P. M., Mircheva Z. I. Investigation of the mutagenic activity of tobacco smoke. Mutat Res. 1987 May;188(1):13–19. doi: 10.1016/0165-1218(87)90109-1. [DOI] [PubMed] [Google Scholar]
  2. D'Agostini F., Bonatti S., Oddera S., De Flora S. Micronuclei in human alveolar macrophages. Respiration. 1992;59 (Suppl 1):35–37. doi: 10.1159/000196102. [DOI] [PubMed] [Google Scholar]
  3. De Flora S., D'Agostini F., Izzotti A., Balansky R. Prevention by N-acetylcysteine of benzo[a]pyrene clastogenicity and DNA adducts in rats. Mutat Res. 1991 Sep-Oct;250(1-2):87–93. doi: 10.1016/0027-5107(91)90165-k. [DOI] [PubMed] [Google Scholar]
  4. De Flora S., Petruzzelli S., Camoirano A., Bennicelli C., Romano M., Rindi M., Ghelarducci L., Giuntini C. Pulmonary metabolism of mutagens and its relationship with lung cancer and smoking habits. Cancer Res. 1987 Sep 1;47(17):4740–4745. [PubMed] [Google Scholar]
  5. De Flora S., Romano M., Basso C., Bagnasco M., Cesarone C. F., Rossi G. A., Morelli A. Detoxifying activities in alveolar macrophages of rats treated with acetylcysteine, diethyl maleate and/or aroclor. Anticancer Res. 1986 Sep-Oct;6(5):1009–1012. [PubMed] [Google Scholar]
  6. Green G. M., Jakab G. J., Low R. B., Davis G. S. Defense mechanisms of the respiratory membrane. Am Rev Respir Dis. 1977 Mar;115(3):479–514. doi: 10.1164/arrd.1977.115.3.479. [DOI] [PubMed] [Google Scholar]
  7. Harris C. C., Hsu I. C., Stoner G. D., Trump B. F., Selkirk J. K. Human pulmonary alveolar macrophages metabolise benzo(a)pyrene to proximate and ultimate mutagens. Nature. 1978 Apr 13;272(5654):633–634. doi: 10.1038/272633a0. [DOI] [PubMed] [Google Scholar]
  8. Izzotti A., Rossi G. A., Bagnasco M., De Flora S. Benzo[a]pyrene diolepoxide-DNA adducts in alveolar macrophages of smokers. Carcinogenesis. 1991 Jul;12(7):1281–1285. doi: 10.1093/carcin/12.7.1281. [DOI] [PubMed] [Google Scholar]
  9. Jahnke G. D., Thompson C. L., Walker M. P., Gallagher J. E., Lucier G. W., DiAugustine R. P. Multiple DNA adducts in lymphocytes of smokers and nonsmokers determined by 32P-postlabeling analysis. Carcinogenesis. 1990 Feb;11(2):205–211. doi: 10.1093/carcin/11.2.205. [DOI] [PubMed] [Google Scholar]
  10. Petrilli F. L., Rossi G. A., Camoirano A., Romano M., Serra D., Bennicelli C., De Flora A., De Flora S. Metabolic reduction of chromium by alveolar macrophages and its relationships to cigarette smoke. J Clin Invest. 1986 Jun;77(6):1917–1924. doi: 10.1172/JCI112520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Petruzzelli S., Bernard P., Paoletti P., Rane A., Giuntini C., Pacifici G. M. Presence of epoxide hydrolase and glutathione S-transferase in human pulmonary alveolar macrophages. Eur J Clin Pharmacol. 1988;34(4):419–421. doi: 10.1007/BF00542447. [DOI] [PubMed] [Google Scholar]
  12. Petruzzelli S., Camus A. M., Carrozzi L., Ghelarducci L., Rindi M., Menconi G., Angeletti C. A., Ahotupa M., Hietanen E., Aitio A. Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients. Cancer Res. 1988 Aug 15;48(16):4695–4700. [PubMed] [Google Scholar]
  13. Phillips D. H., Hemminki K., Alhonen A., Hewer A., Grover P. L. Monitoring occupational exposure to carcinogens: detection by 32P-postlabelling of aromatic DNA adducts in white blood cells from iron foundry workers. Mutat Res. 1988 Mar;204(3):531–541. doi: 10.1016/0165-1218(88)90047-x. [DOI] [PubMed] [Google Scholar]
  14. Rossi G. A., Sacco O., Cosulich E., Damiani G., Corte G., Bargellesi A., Ravazzoni C. Pulmonary sarcoidosis: excess of helper T lymphocytes and T cell subset imbalance at sites of disease activity. Thorax. 1984 Feb;39(2):143–149. doi: 10.1136/thx.39.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rothman N., Poirier M. C., Baser M. E., Hansen J. A., Gentile C., Bowman E. D., Strickland P. T. Formation of polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells during consumption of charcoal-broiled beef. Carcinogenesis. 1990 Jul;11(7):1241–1243. doi: 10.1093/carcin/11.7.1241. [DOI] [PubMed] [Google Scholar]
  16. Vahakangas K., Haugen A., Harris C. C. An applied synchronous fluorescence spectrophotometric assay to study benzo[a]pyrene-diolepoxide-DNA adducts. Carcinogenesis. 1985 Aug;6(8):1109–1115. doi: 10.1093/carcin/6.8.1109. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES