Effect of nanoparticles on the male reproductive system of mice.

The effects of nanoparticles toward on the male reproductive system of mice were investigated. Three sizes (14, 56 and 95 nm) of carbon black nanoparticles were intratracheally administered (0.1 mg/mouse for 10 times every week) to ICR male mice to investigate their adverse effects on the reproductive function. The serum testosterone levels were elevated significantly in the 14- and 56-nm carbon nanoparticles-exposed groups. Histological examination showed partial vacuolation of the seminiferous tubules. In addition, the effects of particle number towards the male reproductive system were investigated. The particle number controlled 14-nm nanoparticles-exposed group (14 N group, which has approximately the same particle number per unit volume as the 56-nm nanoparticles) showed fewer effects than did the 56-nm nanoparticles-exposed groups. These results suggest that carbon nanoparticle-exposure has adverse effects on the mouse male reproductive function. Furthermore, the effects of nanoparticles on the male reproductive system depend on particle mass rather than particle number.

Murine strain differences in 8-hydroxy-deoxyguanosine formation in hepatic DNA induced by oxidized lard and dietary oils.

Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.

Liver carcinogenesis and formation of 8-hydroxy-deoxyguanosine in C3H/HeN mice by oxidized dietary oils containing carcinogenic dicarbonyl compounds.

Oxidized dietary oils (lard, soybean oil, and sardine oil) were orally administered to C3H/HeN male mice. After 6 months, benign hepatocellular adenoma was observed in the mice treated with all three oxidized dietary oils. After 12 months, malignant hepatocellular carcinoma and hepatoblastoma were observed in addition to the benign tumor. Oxidized sardine oil caused the highest tumor incidence (35%) and malignant tumors (27.5%) among the oxidized dietary oils tested. Mice treated with oxidized lard and sardine oil exhibited a significant increase of 8-OH-dG in the livers. The amounts of 8-OH-dG found in the mice treated with oxidized sardine oil correlated with the rates of tumor incidence. After 6 months, mRNA decreased in the case of oxidized lard and sardine oil, whereas it increased in the case of oxidized soybean oil, either in 8-oxoguanine-DNA glycosylase (OGG1) or in 8-oxo-dGTPase. On the other hand, there was no appreciable change in mRNA, in either OGG1 or 8-oxo-dGTPase, after 12 months. Oxidized sardine oil contained the highest level of malonaldehyde (MA) (713+/-91.1 nmol/g) and glyoxal (33.3+/-5.2 nmol/g) among three oxidized oils. The malignant tumor incidence correlated with the high level of MA and glyoxal found in the dietary oils tested.

Development of malignant glioma 15 months after anterior temporal lobectomy in a patient with temporal lobe epilepsy.

We report a 36-year-old woman, who had previously undergone anterior temporal lobectomy for intractable temporal lobe seizures; fifteen months later, magnetic resonance (MR) images showed a space-occupying lesion in the temporal lobectomy cavity. After a second operation, a histopathological examination showed a grade III astrocytoma. The fortuitous co-occurrence of temporal lobe epilepsy and a tumour was suspected, but histopathological and immunohistochemical examination of original resected temporal lobe parenchyma did not show evidence of neoplasm. The patient had not undergone postoperative radiotherapy and had not experienced viral infections. We propose that two factors possibly associated with the development of glioma were chemical exposure from anticonvulsant agents and trauma from resection of the anterior temporal lobe during initial surgery.

The effect of dietary carotenoids on lung tumorigenesis induced by intratracheally instillated diesel exhaust particles.

The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.

Effect of the natural antioxidant 2"-O-glycosylisovitexin on superoxide and hydroxyl radical generation.

The inhibitory effect of 2"-O-glycosyl isovitexin (2"-O-GIV) isolated from green barley leaves on superoxide and hydroxyl radical generation was investigated using electron spin resonance spectroscopy. 2"-O-GIV exhibited dose-related inhibitory activity both towards superoxide generation and hydroxyl radical generation. 2"-O-GIV inhibited superoxide formation by 97% at a level of 25 mM and inhibited hydroxyl radical formation by 91% at a level of 500 microM. The results suggest that the inhibitory activity of 2"-O-GIV is due to trapping radicals.

Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens.

In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.

Manipulation of the L-arginine-nitric oxide pathway in airway inflammation induced by diesel exhaust particles in mice.

The role of the L-arginine-nitric oxide (NO) pathway in bronchial asthma that is characterized by eosinophilic airway inflammation has not yet been established. We investigated the effects of three different agents on eosinophilic airway inflammation induced by the intratracheal instillation of diesel exhaust particles (DEP) in mice: L-Arginine, the substrate for NO synthases; L-N(G)-nitro-L-arginine methyl ester (L-NAME), a relatively selective inhibitor of constitutive NO synthase; and aminoguanidine, a relatively selective inhibitor of inducible NO synthase. The mice received drinking water with or without added drug for a continuous period of 9 weeks plus 4 days. Lung histology showed that airway inflammation with goblet cell proliferation induced by DEP was aggravated by the administration of L-arginine or L-NAME, whereas it was reduced by aminoguanidine. The numbers of neutrophils around the airways in animals that received plain drinking water, L-arginine, L-NAME, and aminoguanidine were 0.98+/-0.26, 3.66+/-0.81, 1.64+/-0.31, and 0.12+/-0.04 (number/mm basement membrane), respectively. The numbers of eosinophils around the airways were 0.37+/-0.08, 16.1+/-6.47, 11.1+/-3.59, and 0.21+/-0.11, respectively. The numbers of goblet cells in the bronchial epithelium were 1.67+/-0.80, 16.5+/-7.33, 19.0+/-3.40, and 0.86+/-0.41, respectively. The cellular profiles of the bronchoalveolar lavage fluid also showed that airway inflammation induced by DEP was aggravated by the administration of L-arginine or L-NAME, whereas it was reduced by aminoguanidine. These results suggest that NO produced from inducible NO synthase may have a detrimental effect on the DEP-induced airway inflammation. A relatively selective inhibition of inducible NO synthase by aminoguanidine may have therapeutic value in the inhalant injury. NO derived from constitutive NO synthase may afford protection against the airway inflammation induced by DEP.

Inhalation of diesel exhaust enhances allergen-related eosinophil recruitment and airway hyperresponsiveness in mice.

We have previously shown that intratracheal instillation of suspension of diesel exhaust particles enhances allergen-related eosinophilic airway inflammation, airway hyperresponsiveness, and local expression of interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present study was designed to elucidate the effects of daily inhalation of diesel exhaust (DE) on the allergen-related respiratory disease. ICR mice were exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen-related eosinophil recruitment to the submucosal layers of the airways and to the bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the lung in a dose-dependent manner compared to exposure to clean air. There were strong correlations between the number of eosinophils in bronchoalveolar lavage (BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue supernatants. In addition, the increases in eosinophil recruitment and local cytokine expression were accompanied by goblet cell proliferation in the bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In contrast, the control mice exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no eosinophil recruitment to the submucosal layers of the airways nor to the bronchoalveolar space and few goblet cells in the bronchial epithelium. The present study provides experimental evidence that daily inhalation of DE can enhance allergen-related respiratory diseases such as allergic asthma. This effect may be mediated by the enhanced local expression of IL-5 and GM-CSF. Increased ambient levels of DE may be implicated in the increasing prevalence of bronchial asthma in recent years.

[Tumor volume and percent of gland involvement with tumor as predictors of pathological stage in prostate cancer].

BACKGROUND: It is well recognized that tumor volume correlates with pathological stage, histological grade and progression in prostate cancer. We analyzed the tumor volume and the percent of gland involvement with tumor (%TV/PV) to determine if either or both of these morphometric factors would be good predictors of pathological stage. METHODS: The pathological reviews were retrospectively performed on the basis of the 22 step sectioned prostate specimens removed by radical retropublic prostatectomy for clinical T1c-T2-T3 prostate cancer. The percent of gland involvement with tumor was calculated using the following formula [100 x (tumor volume cc/prostate volume cc)]. When the patients had organ confined disease (OCD) or specimen confined disease (SCD) they were defined as surgically cured patients, whereas the patients with positive surgical margin, seminal vesicle involvement or positive lymph node were defined as not surgically cured patients. RESULTS: The likelihood of OCD was 25% in patients with clinical T1c-T2 disease. No patients with clinical T3 had OCD. Patients with SCD was not observed. The mean tumor volume was 1.3 cc in the surgically cured patients and 6.2 cc in the not surgically cured patients. The tumor volume correlated with pathological stage (r = 0.607, p = 0.0054). The mean %TV/PV was 3.23% in the surgically cured patients and 18.2% in the not surgically cured patients. The %TV/PV also correlated with pathological stage (r = 0.543, p = 0.0129). Both the tumor volume and the %TV/PV in surgically cured patients were less than those in the not surgically cured patients. A correlation between tumor grade and both the tumor volume and the %TV/PV were not observed. CONCLUSION: The tumor volume and the %TV/PV correlated well with the final pathological stage. Multiple regression analysis showed that the tumor volume was the best predictor of pthological stage.

Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles.

In order to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), the relationship between lung tumour response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA was examined. The role of high dietary fat and beta-carotene on these responses was also studied. Mice were intratracheally injected with 0.05, 0.1 and 0.2 mg of DEP per animal once weekly for 10 weeks. After 12 months, the lung tumour incidence in mice treated with 0.05 mg and 0.1 mg showed similar increases (30% and 31%), but was decreased to 24% at 0.2 mg. High dietary fat enhanced the incidence of both benign and malignant tumours. beta-carotene partially prevented the tumour development. After the 10 weekly treatments of DEP, inflammatory reaction was observed in the respiratory tract and alveoli. The formation of 8-OHdG in lung DNA from mice treated with DEP showed a dose dependent increase. 8-OHdG formation was enhanced by high dietary fat and partially reduced by beta-carotene. Formation of 8-OHdG was significantly correlated with the lung tumour incidence except at 0.2 mg. These results suggest that the induction of oxidative DNA damage may be an important factor in the initiation of DEP-induced lung carcinogenesis, and that beta-carotene and high dietary fat may play a role in the regulation of tumour development via modulation of the formation of 8-OHdG.

Oxygen radicals in lung carcinogenesis accompanying phagocytosis of diesel exhaust particles.

We sought to examine the involvement of oxygen radicals derived from phagocytosis process in lung carcinogenesis induced by diesel exhaust particles (DEP). The carcinogenic response and formation of 8-hydroxydeoxyguanosine (8-OHdG) were examined in the lungs of mice intratracheally injected with washed DEP (WDEP), DEP, or nontoxic control particles of titanium dioxide (TiO2). After 10 weekly treatments with these particles, the formation of 8-OHdG in the lungs of mice treated with WDEP or DEP showed a significant increase, but not in those treated with TiO2. After 12 months, the incidence of lung tumors in mice treated with WDEP or DEP was higher than that of mice treated with vehicle by 2.3- and 3.1-fold, respectively. A significant difference in the incidence of tumors was found between the vehicle group and DEP-treated group. Treatment with TiO2 had no effect on the incidence of lung tumors. The formation of 8-OHdG in mice treated with these particles was significantly correlated with the development of lung tumors. These results suggest that the induction of DNA damage by oxygen radicals may be an important factor in the initiation of WDEP- and DEP-induced lung carcinogenesis, and that oxygen radicals derived from the phagocytic process may play a role in 8-OHdG formation induced by DEP.

[Impact of androgen deprivation prior to radical prostatectomy for T1, T2 prostate cancer on the likelihood of curative surgery].

BACKGROUND: Extracapsular extension is commonly seen in patients undergoing radical prostatectomy for localized prostate cancer due to understaging of disease. One possible approach to reduce the likelihood of extracapsular disease is androgen deprivation prior to radical prostatectomy, neoadjuvant therapy. However, adequate application is not clear. We analyzed the outcome of neoadjuvant therapy and radical prostatectomy in an attempt to expand our understanding on indications of neoadjuvant therapy. METHODS: Forty-six selected patients with clinical T1 or T2 prostate cancer were retrospectively reviewed. Twenty-two patients underwent neoadjuvant therapy (group N) that mainly consists of LH-RH agonist. The duration of neoadjuvant therapy, varied from 1 to 12 months with the mean being 4 months. Twenty-four underwent radical prostatectomy alone (group S). RESULTS: In the group N and group S, 59% and 33% had either organ confined disease (OCD) or specimen confined disease (SCD) respectively. When the patients had OCD or SCD, they were defined as surgically cured patients. In the patients with clinical stage T1b, T1c, and T2 disease, likelihood of surgical cure were 100%, 50%, 46.7% in group N, 100%, 20%, 11%, in group S respectively. In the patients with initial serum PSA less than 10 ng/ml and more than 10.1 ng/ml, likelihood of surgical cure were 83.3% and 50% in group N, 63.6% and 15.4% in group S, respectively. Likelihood of surgical cure was higher in the patients with well differentiated carcinoma both in group N and group S. All the patients with serum PSA less than 0.1 ng/ml after neoadjuvant therapy had OCD. CONCLUSION: Neoadjuvent therapy could be beneficial either in the patients with moderately or in the poorly differentiated adenocarcinoma of prostate especially in the group with initial serum PSA more than 10.1 ng/ml. However, in patients both with well differentiated adenocarcinoma and the initial serum PSA less than 10 ng/ml, no evidence of beneficial effect on the likelihood of OCD or SCD was observed. PSA after neoadjuvant therapy could be useful predictor for the pathological outcome.

Immunohistochemical localization of surfactant protein A in N-bis (2-hydroxypropyl) nitrosamine-induced lung tumors in rats.

Surfactant protein A (SP-A) is most abundant protein associated with pulmonary surfactant which is synthesized by alveolar type II cells in the alveoli. In this study, we localized SP-A in experimentally induced pulmonary hyperplasias and tumors in rats, by immunohistochemistry. When rats were given a single intraperitoneal injection of N-bis (2-hydroxypropyl) nitrosamine (BHPN) followed by exposed to mixture gases of O3 and NO2, hyperplastic alveolar type II cells stained with the antibody against SP-A were located in the alveolar walls near the alveolar ducts. Adenomas and adenocarcinomas were stained with the anti-SP-A antibody in the lung parenchyma. These immunohistochemical findings suggested that the lung tumors induced in rats treated with BHPN and additionally exposed to mixture gases of O3 and NO2 are derived from mainly alveolar type II cells.

Formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine, in mouse lung DNA after intratracheal instillation of diesel exhaust particles and effects of high dietary fat and beta-carotene on this process.

Diesel exhaust particles (DEP) cause tumors in the respiratory tracts of experimental animals. It was previously shown that DEP produced superoxide and hydroxyl radical. To examine whether oxygen radicals are involved in mouse lung tumorigenesis induced by DEP, formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine (oh8dG), by DEP was investigated. Furthermore, the role of high dietary fat and beta-carotene on this process was studied. After intratracheal instillation of DEP, a significant increase of oh8dG in mouse lung DNA was observed. High dietary fat enhanced the formation of oh8dG in lung DNA. Intake of beta-carotene suppressed the formation of oh8dG in lung DNA, but the protective effect of beta-carotene against this process was not statistically significant. These results suggest that formation of oh8dG in lung DNA was induced by oxygen free radicals produced by DEP. Thus, it is possible that oh8dG is a promutagenic lesion in DEP-induced lung tumorigenesis in mice and high dietary fat enhances this process through the generation of oh8dG in mouse lung DNA.

[A case of necrotizing sarcoid granulomatosis diagnosed by open lung biopsy].

A 59-year-old man had an abnormal shadow on chest X-ray film. He was admitted to Tohoku-chuou Hospital, and a lung lesion in the right lower lobe was diagnosed as a benign nodule. A new nodular lesion appeared on a chest X-ray film taken two months after his discharge from the hospital. Both lesions were in the same lobe; the older one was in segment 9 and the newer one was in segment 10. For the lesion in segment 10, malignancy was not ruled out, so open lung biopsy (right lower lobectomy) was done. With the findings of angitis and focal necrosis surrounded by granulomas consisting of epthelioid cells and multinuclear giant cells, the new lesion in segment 10 was diagnosed as necrotizing sarcoid granulomatosis. The older lesion in segment 9 was a tuberculoma. We conclude that in this case the open lung biopsy was necessary to diagnose necrotizing sarcoid granulomatosis in lung.

[Anesthetic management of a patient with a history of right upper lobectomy for esophageal resection via left thoracotomy].

We anesthetized a patient for esophageal resection in a right lateral decubitus position, because of his right pleural adhesion after lobectomy for tuberculosis. Although hypoxemia was expected on left lung compression during the surgery, oxygenation was not compromised. A good ventilation/perfusion relationship might have been maintained in both the right and left lungs during the procedure.

Gas chromatographic determination of vapor-phase biomarkers formed from rats dosed with CCl4.

Sprague-Dawley rats dosed with CCl4 (3 ml kg-1) were placed in a glass chamber through which air was passed continuously at a rate of 60 ml min-1. Volatile aldehydes and ketones in expired air from rats were derivatized to thiazolidines by passing the effluent gas stream through an aqueous cysteamine solution. The thiazolidine derivatives were then extracted and analyzed by gas chromatography with a nitrogen-phosphorus detector and gas chromatography/mass spectrometry. The compounds identified were formaldehyde, acetaldehyde, acetone and formyl chloride. There were no appreciable differences in levels of formaldehyde and acetaldehyde between CCl4-dosed rats and control rats, whereas the levels of acetone in CCl4-dosed rats showed an increase compared to those in control rats. Results suggest that acetone is the major volatile carbonyl compound produced following acute doses of CCl4. Results of thiobarbituric acid assay on the livers from a control rat and a CCl4-dosed rat did not show any appreciable differences.

[Immunological effect of recombinant interferon-gamma in renal cell carcinoma].

The immunological effect of interferon-gamma (IFN-gamma) was investigated in 18 cases of renal cell carcinoma before and after the operation. In 6 patients, IFN-gamma was administered preoperatively for 21 days (administration group), while 12 patients underwent nephrectomy alone without preoperative treatment (control group). The peripheral immunological effects were measured at before and 12 days after the operation in the administration group and at 11 days in the control group. In the administration group, a marked increase was noted in the test of antibody dependent cell-mediated cytotoxicity (ADCC) activity and natural killer (NK) activity, and slight increase in CD4/8 and CD11b. In low stage cases, no appreciable effect was obtained by the administration of IFN-gamma. However, in high stage cases, IFN-gamma tended to increase the value of ADCC activity and NK activity. Immunohistochemical studies of tumor infiltrating lymphocytes in renal cell carcinoma showed a high incidence of CD8 and CD11b in the administration group. Moreover, the presence of CD8 was higher than that of CD4 in the administration group in contrast to the results of the peripheral blood analysis.

Combined exposure to NO2, O3 and H2SO4-aerosol and lung tumor formation in rats.

The promoting effects of a combined exposure to two pollutants (NO2, O3 or H2SO4-aerosol) at near ambient levels on lung tumorigenesis induced by N-bis(2-hydroxypropyl) nitrosamine (BHPN) were investigated in male Wistar rats. The rats were given a single intraperitoneal injection of BHPN (0.5 g per kg body wt.) at 6 weeks of age. They then were exposed to clean air, 0.05 ppm O3 (mean concentration for 10 h/day; 0.1 ppm peak concentration), 0.05 ppm O3 (mean concentration for 10 h/day; 0.1 ppm peak concentration) + 0.4 ppm NO2 or 0.4 ppm NO2 + 1 mg/m3 of H2SO4-aerosol for 13 months and were then maintained in a clean room for another 11 months. Room control animals were kept after injection of BHPN in a clean room for 24 months. The incidence of primary lung tumors in rats exposed to 0.05 ppm O3, 0.05 ppm O3 + 0.4 ppm NO2 and 0.4 ppm NO2 + 1 mg/m3 of H2SO4-aerosol with BHPN treatment was 8.3% (3 out of 36 rats), 13.9% (5 out of 36 rats) and 8.3% (3 out of 36 rats), respectively. The tumors were adenomas and adenocarcinomas. The incidence of adenomas was 2.8% (1 out of 36 rats) in the O3 alone group, 11% (4 out of 36 rats) in O3 + NO2 group and 5.6% (2 out of 36 rats) in NO2 + H2SO4 group. The incidence of adenocarcinomas was 5.6% (2 out of 36 rats) in the O3 group, 2.8% (1 out of 36 rats) in O3 + NO2 group and 2.8% (1 out of 36 rats) in NO2 + H2SO4 group. No lung tumors were found in the rats exposed to clean air with BHPN treatment and in animals not given BHPN but exposed to each air pollutant. The difference in tumor incidence between the clean air group with BHPN and the O3 + NO2 group with BHPN was statistically significant. The results show that exposure to O3 alone enhances tumor development and that the combined exposure to O3 or H2SO4 with NO2 produces an additional increase in incidence of lung tumor, respectively. The incidence of slight-moderate to marked alveolar cell hyperplasia in the groups exposed to each air pollutant with BHPN treatment was higher than that in the groups exposed to clean air with BHPN. Exposure to each air pollutant had no effect on the development of bronchiolar mucosal hyperplasia in lungs of rats treated with BHPN.(ABSTRACT TRUNCATED AT 400 WORDS)