BIOMARKER ALTERATIONS PRODUCED IN RAT LUNG BY INTRATRACHEAL INSTILLATIONS OF AIR PARTICULATE EXTRACTS AND CHEMOPREVENTION WITH ORAL N-ACETYLCYSTEINE

Organic matter extracts were obtained from particulates recovered from 10,000-m(3) air samples collected in Sicily (Italy). The overall conc entrations of acenaphthene, benzo(a)pyrene, phenanthrene, anthracene, fluoranthene, and pyrene were 526 ng/m(3) air in a highly polluted urb an area and 48 ng/m(3) in a rural area affected by motor vehicle traff ic pollution, After metabolic activation, both samples were mutagenic in Salmonella typhimurium his strains of the TA and YG series, with po tencies in TA100 of 140.7 and 11.8 revertants/m(3) air, respectively. The samples, resuspended in tricaprylin, were instilled intratracheall y in Sprague-Dawley rats for 5 consecutive days, accounting for a cumu lative dose in each animal of the organic fractions extracted from 400 m(3) air, which corresponds approximately to the volume of air inhale d by a man in 1 month. Treatment with the rural area sample and, at hi gher levels, with the urban area sample resulted in the formation of a dducts to lung DNA, as assessed both by synchronous fluorescence spect rophotometry and by P-32 postlabeling, which showed the appearance of up to six individual adducts emerging from diffuse diagonal radioactiv e zones. The adducts mere more efficiently detected by extraction with butanol than by digestion with nuclease P1. DNA binding of air partic ulate extracts was followed by alterations of early damage biomarkers only in the rats treated with the urban area sample. Repair of DNA dam age in lung cells was inferred from a significant stimulation of the n uclear enzyme poly(ADP-ribose) polymerase compared with that in sham-e xposed rats. Among the cells recovered by bronchoalveolar lavage, an i ncrease in polymorphonucleate leukocytes and cells of the ciliated res piratory epithelium was accompanied by a relative decrease in pulmonar y alveolar macrophages. The frequency of micronuclei was significantly enhanced both in epithelial cells and alveolar macrophages, and binuc leated macrophages were also more frequent in treated rats. The thiol N-acetylcysteine, one of the most promising cancer chemopreventive age nts, was administered with drinking water to a group of animals receiv ing the air particulate polycyclic aromatic hydrocarbon fraction from the urban area. N-acetylcysteine prevented or considerably attenuated the alterations of all monitored parameters. These findings provide ev idence that, even under outstandingly high exposure conditions, it is possible to protect the respiratory tract from DNA-binding and DNA-dam aging air particulate carcinogens.