Increased life span and decreased weight in hamsters exposed to cigarette smoke.

Five groups of fifty-one 2-month-old male Syrian golden hamsters received three 10-minute exposures to cigarette smoke per day, 5 days per week, for the duration of their lives. Three of the groups were also chronically exposed to aerosols of chrysotile asbestos, cobalt oxide, and nickel oxides, respectively. The fourth group received twelve weekly injections of 0.25 mg of diethylnitrosamine. The smoke-exposed groups lived significantly (P less than .01) longer than their sham-exposed cohorts and untreated controls. Their mean body weights were significantly (P less than .01) lower than in the sham-exposed groups. The hypothesis is proposed that delayed onset of amyloidosis and lower body weight in the smoke-exposed hamsters may have been responsible for their increased life spans. It is hypothesized that cigarette smoke affected the immune system of the animals, resulting in retardation of amyloidosis, a frequent cause of death in hamsters.     

Increased Life Span and Decreased Weight in Hamsters Exposed to Cigarette Smoke

Five groups of fifty-one 2-month-old male Syrian golden hamsters received three 10-minute exposures to cigarette smoke per day, 5 days per week, for the duration of their lives. Three of the groups were also chronically exposed to aerosols of chrysotile asbestos, cobalt oxide, and nickel oxides, respectively. The fourth group received twelve weekly injections of 0.25 mg of diethylnitrosamine. The smoke-exposed groups lived signficantly (P <.01) longer than their sham-exposed cohorts and untreated controls. Their mean body weights were significantly (P < .01) lower than in the sham-exposed groups. The hypothesis is proposed that delayed onset of amyloidosis and lower body weight in the smoke exposed hamsters may have been responsible for their increased life spans. It is hypothesized that cigarette smoke affected the Immune system of the animals, resulting in retardation of amyloidosis, a frequent cause of death in hamsters.     

Chronic inhalation exposure of hamsters to nickel-enriched fly ash

Hamsters were chronically exposed to ～70 μg/liter respirable nickel-enriched fly ash (NEFA) aerosol, ～17 μg/liter NEFA, or ～70 μg/liter fly ash (FA) for up to 20 months. A control group received sham exposures. The NEFA particles of respirable size contained approximately 6% nickel, compared to about 0.3% for FA. Five hamsters/group were sacrificed after 4, 8, 12, or 16 months of exposure. An additional five hamsters/group were withdrawn from exposure at the same intervals for lifelong observations. Exposures to NEFA had no significant effect on body weight and life span of the animals although heavy deposits of NEFA in the lungs were demonstrated. However, lung weights of the high NEFA- and of the FA-exposed animals were significantly higher than those of the low-NEFA group and the controls, and mean lung volumes were significantly larger for the high-NEFA group and the FA group than for the low-NEFA group and the controls. Dust was deposited (anthracosis) in the lungs of all exposed hamsters. Incidence and severity of interstitial reaction and bronchiolization were significantly higher in the dust-exposed groups than in the sham-exposed controls. The severity of anthracosis, interstitial reaction, and bronchiolization was significantly lower in the low-NEFA group than in the high-NEFA and FA groups. While two malignant primary thorax tumors were found in two hamsters of the high-NEFA group, no statistically significant carcinogenesis was observed. Of the exposure-related changes, only anthracosis decreased after withdrawal from exposure. Pulmonary nickel burdens after 20 months of exposure suggest that the pulmonary clearance rate was slower in the high-NEFA group than in the low-NEFA group.     

Effect of cigarette smoking and/or N-bis(2-hydroxypropyl)nitrosamine (DHPN) on the development of lung and pleural tumors in rats induced by administration of asbestos

Occupationally induced lung cancer and mesothelioma have long been attributed to asbestos and moreover, several epidemiological studies have indicated a co-carcinogenic effect of cigarette smoking on the incidence of lung cancer in asbestos workers. The aim of the present study was to investigate the co-carcinogenic effects of asbestos and other carcinogens with emphasis placed on determining the effects of cigarette smoking on the incidence of asbestos induced carcinomas. Doses of 15 mg of chrysotile asbestos were administered intratracheally to Wistar rats alone and in conjunction with N-bis(hydroxypropyl)nitrosamine (DHPN) and/or cigarette smoking. DHPN at dose of 1 g/kg/B.W. was injected three times intraperitoneally, and the subject animals were exposed to smoke from 10 cigarettes per day, six days a week, for their entire life span. As a result, lung carcinomas were induced in one out of the 31 rats receiving only asbestos. Lung tumors were induced at a much higher incidence in the groups receiving DHPN alone and in conjunction with asbestos: of the 37 rats treated with DHPN alone 19 (51.4%) developed lung tumors, whereas those receiving asbestos as well showed an incidence of 68.4% (23/38) of carcinomas. The development of lung carcinomas (including adenocarcinomas, epidermoid carcinomas, anaplastic carcinomas, and combined carcinomas) was seen in 8 (21.6%) out of the 37 rats receiving DHPN alone and in 23 (60.5%) out of the 38 rats receiving asbestos as well. The incidence of lung carcinoma was significantly increased in combined treatment with asbestos than DHPN alone. In the group receiving asbestos in combination with cigarette smoke, 4 (13.8%) out of the 29 rats developed lung carcinomas, but these carcinomas were more common than in the group receiving only asbestos. Moreover, in the group administered asbestos, DHPN and smoking combined, lung tumors developed in 18 (62.1%) out of the 29, 15 (51.7%) of which proved to be malignant. Mesothelioma (pleura) was induced in three groups in the following combinations: DHPN plus asbestos, 8/38 (21.1%); smoking plus asbestos, 2/29 (6.9%); and smoking, DHPN and asbestos, 4/29 (13.8%). These tumors were extensively located, that is, on the parietal pleura, visceral pleura, epicardium and diaphragm surface. However, mesothelioma was not induced by asbestos alone nor by DHPN alone. Carcinogenicity of asbestos for pleural tumors was significantly promoted by combined treatment with DHPN to an extent greater than DHPN alone. It should be noted that asbestos plus smoking resulted in a higher incidence of mesothelioma than asbestos alone.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute and subchronic inhalation exposures of hamsters to nickel-enriched fly ash.

One 6-hr inhalation exposure of hamsters to Ni-enriched fly ash (NEFA) aerosol (respirable aerosol concentration ～200 μg/liter) deposited about 80 μg in the deep lung, of which 75 μg was still present 30 days postexposure. The animals tolerated the exposure well during the 30-day postexposure observation period.Two-month exposures of hamsters to NEFA or fly ash (FA) aerosols (～185 μg/liter) resulted in a deep lung burden of about 5.7 mg, dark discoloration of lungs, heavily dustladen macrophages, and significantly higher lung weights than in controls, but only minimal inflammatory reaction and no deaths. There was no difference between NEFA and FA effects. The NEFA contained 9% Ni; FA contained 0.03% NI.The results of this study indicate low acute and subchronic toxicity and slow lung clearance of NEFA and FA.     

Asbestos cement dust inhalation by hamsters.

Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation (A. P. Wehner, G. E. Dagle, and W. C. Cannon, 1978, Environ. Res. 16, 393-407). The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.     

Estimation of the diesel exhaust exposures of railroad workers: I. Current exposures

As a part of a series of epidemiological studies of railroad workers, measurements were made to characterize workers' exposures to diesel exhaust. Since diesel exhaust is not a single compound, an exposure marker was sought. The personal exposures to respirable particulate matter (RPM) of over 530 workers in 39 common jobs were measured in four U.S. railroads over a three-year period. Significant amounts of cigarette smoke (20–90%) were found in many of these samples. Therefore, the respirable particulate concentration, adjusted to remove the fraction of cigarette smoke (ARP), was chosen as a marker of diesel exhaust exposures. The geometric mean exposures to ARP ranged from 17 μg/m³ for clerks to 134 μg/m³ for locomotive shop workers. Significant interrailroad variations were observed in some job groups indicating that the different facilities, equipment, and work practices found among the railroads can affect a worker's exposure to diesel exhaust. Climate was also found to have a significant effect on exposure in some job groups.     

Pathological Changes Associated with the Inhalation of Sodium Zirconium Lactate

This investigation concerned the use of quantitative risk assessment for estimating cancer mortality at low-level exposures. We empirically tested whether extrapolating by linear no-threshold models predicted implausible risks at low-level exposures. Cadmium in cigarette smoke was the low-level exposure, and extrapolation was based on potencies estimated from an occupational study and a rodent cancer bioassay. Inhaled cadmium in mainstream and sidestream smoke was estimated from published laboratory experiments. Smoking-specific lung cancer and all-cause mortality rates were estimated from large population-based studies. The mortality rates, amount of inhaled cadmium, and potency values were used to construct life tables for calculating lifetime lung cancer risk with and without a contribution from cadmium in cigarette smoke. The epidemiologic data predicted that 1 to 18 lung cancer deaths per 10 000 smokers may be attributable to inhaled cadmium in cigarette smoke, or approximately 0.2% to 1.6% of smoking-induced lung cancer deaths. Upper 95% bounds on these figures are 7 to 95 lung cancer deaths or 1.6% to 8.8% of smoking-related deaths. The rodent data predicted that 80 to 416 lung cancer deaths per 10 000 smokers (95% upper bounds: 136–707) or 13% to 47% (23–81%) of smoking-induced lung cancer mortality may be attributable to cadmium in cigarette smoke. Linear extrapolation from human data appears to provide plausible estimates of risk at low doses. Considering the large number of carcinogens present in cigarette smoke, the extrapolation from rodents appears to overestimate human risks. Whether this discrepancy results from differences in potency for cadmium chloride aerosol as opposed to cadmium in particulate form, or from humans having greater sensitivity to cadmium's carcinogenic effect, or both, remains unclear.     

Pulmonary tissue and cigarette smoke: 1. Cellular response to hydrocortisone

Hydrocortisone acetate (HCA) administration significantly reduces the population of pulmonary macrophages and blood leukocytes in control, sham-treated, and smoke-exposed $\text{C57BL}\text{6J}$ mice. This treatment impedes markedly the influx of macrophages from bone marrow into the lungs. The small number of new phagocytes noted in lungs following HCA treatment appears to arise by proliferation of in situ pulmonary macrophages. Mortality rate of sham-treated and smoke-exposed mice was approximately twice that of control animals following HCA treatment. While severe pulmonary disorders were noted in lungs of HCA-treated, smoke-exposed animals, considerably milder abnormalities were seen in lungs of sham-treated mice. The data reported indicate that physical stress generated by manipulation during sham and smoke treatment, exposure to cigarette smoke, and reduction of pulmonary macrophages and leukocyte populations by HCA administration are factors which adversely affect pulmonary integrity and survival time of the animals.     

Reaction of macrophages to cigarette smoke. II. Immigration of macrophages to the lungs.

The present study identifies the source of the elevated pulmonary macrophage population in young adult male mice which results when animals are exposed to cigarette smoke. Light microscopic and autoradiographic analysis of pulmonary tissue from smoke-exposed animals revealed that pulmonary macrophages (free, attached, and septal or interstitial) divide only rarely. Further, it was noted that, during the marked progressive increase in the labeled macrophage population in the lungs, the number of silver grains over the nuclei of labeled macrophages did not become significantly diluted. Thus, the markedly elevated macrophage population which results when animals are exposed to cigarette smoke appears, for the most part, to be due to immigration of cells from bone marrow rather than in situ division of resident macrophages.     

Reaction of Macrophages to Cigarette Smoke. II. Immigration of Macrophages to the Lungs

The present study identifies the source of the elevated pulmonary macrophage population in young adult male mice which results when animals are exposed to cigarette smoke. Light microscopic and autoradiographic analysis of pulmonary tissue from smoke-exposed animals revealed that pulmonary macrophages (free, attached, and septal or interstitial) divide only rarely. Further, it was noted that, during the marked progressive increase in the labeled macrophage population in the lungs, the number of silver grains over the nuclei of labeled macrophages did not become significantly diluted. Thus, the markedly elevated macrophage population which results when animals are exposed to cigarette smoke appears, for the most part, to be due to immigration of cells from bone marrow rather than in situ division of resident macrophages.     

The pathological effects of prolonged asbestos ingestion in rats

The effects of prolonged ingestion of amosite, crocidolite, and chrysotile UICC standard reference asbestos samples were examined in groups of laboratory rats. Animals were given over 250 mg per week for periods up to 25 months and were monitored for the remainder of their life span. Animals were examined for evidence of pathological effects and gastrointestinal mucosal cytokinetic disturbances and for signs of penetration and dissemination of fiber. There was no excess of malignant tumors in the experimental groups when compared with control animals, and no gastrointestinal mucosal abnormalities were found. An examination of the cytokinetic status of a subgroup of animals exposed to asbestos similarly showed no evidence of any adverse effects of prolonged ingestion of amosite asbestos fiber. Detailed electron microscopic examination of various tissue residues for the presence of asbestos fibers was also undertaken. No penetration and/or damage to any of the gut tissues was found. Although occasional fibers were found in a variety of tissue residues, there was no evidence of preferential retention of fibers within any specific tissue and no sign of higher fiber burdens in those animals with tumors. It was concluded that there were no significant adverse effects of prolonged asbestos ingestion in healthy laboratory rats. The implications of these findings are discussed in the light of other published work.     

Inhalation Studies With a Glycol Complex of Aluminum-Chloride-Hydroxide

Inhalation studies were performed with a propylene glycol complex of aluminum-chloride-hydroxide (alchlor), a compound found in some aerosol antiperspirant preparations. Hamsters were given either three exposures to 150 mg alchlor/cu meter or 30 exposures to 50 mg/cu meter and killed at various times for histopathological examination. The lungs of animals given 20 or more exposures to 50 mg/cu meter showed a granulomatous lesion in the respiratory bronchioles that persisted throughout a six-week postexposure period. Alveolar thickening and increased numbers of macrophages were seen in lungs of hamsters soon after three exposures to 150 mg/cu meter but with time these changes regressed. Lung weights in hamsters given three exposures to 35 mg/cu meter or higher were increased on the fourth day.

Mixed function oxidase (MFO) activities of rabbit and hamster microsomes from both lung and liver were examined after three daily exposures. No changes were seen in the MFO activity of liver microsomes. Lung microsomes from exposed animals showed a decrease in specific activity (per milligram microsomal protein). However, lung weights of exposed animals were increased, and the activity per lung was similar in exposed and control animals.     

石棉与烟雾溶液对人肺肺细胞DNA的损伤作用

目的 探讨石棉与烟雾溶液联合作用对人胚肺细胞ＤＮＡ的损伤作用。方法 采用非程序ＤＮＡ合成试验，对石棉与烟雾溶液单独及联合作用时人胚肺细胞ＤＮＡ修复合成情况进行了观察。     

A passive tobacco smoke exposure system for laboratory animals

A simple passive tobacco smoke exposure system was developed for laboratory animals. The system consisted of a tobacco smoke generator and an exposure chamber. Performance testing was conducted using Fischer 344 rats. The rats were exposed to passive tobacco smoke generated by 20 cigarettes per day for 3 months. The concentration of the cigarette smoke aerosol (particle phase) in the chamber can be kept almost constant during exposure. The daily average mass concentration was 10.0 +/- 4.3 mg/m3 and the carbon monoxide was 79 +/- 22 ppm during exposure.     

Exposure to mosquito coil smoke may be a risk factor for lung cancer in Taiwan

Background

About 50% of lung cancer deaths in Taiwan are not related to cigarette smoking. Environmental exposure may play a role in lung cancer risk. Taiwanese households frequently burn mosquito coil at home to repel mosquitoes. The aim of this hospital-based case-control study was to determine whether exposure to mosquito coil smoke is a risk for lung cancer.

Methods

Questionnaires were administered to 147 primary lung cancer patients and 400 potential controls to ascertain demographic data, occupation, lifestyle data, indoor environmental exposures (including habits of cigarette smoking, cooking methods, incense burning at home, and exposure to mosquito coil smoke ), as well as family history of cancer and detailed medical history.

Results

Mosquito coil smoke exposure was more frequent in lung cancer patients than controls (38.1% vs.17.8%; p<0.01). Risk of lung cancer was significantly higher in frequent burners of mosquito coils (more than 3 times [days] per week) than nonburners (adjusted odds ratio = 3.78; 95% confidence interval: 1.55-6.90). Those who seldom burned mosquito coils (less than 3 times per week) also had a significantly higher risk of lung cancer (adjusted odds ratio = 2.67; 95% confidence interval: 1.60-4.50).

Conclusion

Exposure to mosquito coil smoke may be a risk factor for development of lung cancer.Key words: Air Pollutants, Lung Neoplasms, Mosquito Coil, Smoke     

Disability Benefits

A bioassay has been developed and used to quantitatively characterize the effects of cigarette smoke on ciliary function. Diluting smoke from 50% (40 ml) to 3% (2.5 ml) increases the number of four-second exposures required for 90% to 100% inhibition from 8 to 80 (or more) puffs. A high degree of correlation and notable similarity in slope of dose-response curves was found for regular cigarettes, cellulose acetate filter cigarettes, and cigarettes with filters of cellulose acetate with activated carbon.

A 50% reduction (dose required to inhibit particle transport rate to 50% of control rate [ED₅₀]) in transport activity was observed with 8 ml (one to ten dilution) of nonfiltered cigarette smoke after eight exposures of four seconds each, delivered at one-minute intervals. The ED₅₀ for hydrogen cyanide under similar conditions was attained at 10μg per puff or at concentrations lower than those reported in smoke. Recovery from HCN was more rapid than after cigarette smoke. Smoke from cigarettes with filters containing activated carbon was found to be less ciliatoxic and contained lower levels of HCN and acrolein.     

The effect of long-term exposure to cigarette smoke on the height and specificity of the secondary immune response to influenza virus in a murine model system.

The effect of long-term exposure to cigarette smoke on the height and specificity of the secondary humoral immune response to influenza was investigated in a murine model system. It was shown that if mice were pre-immunized with a sub-lethal infection of influenza virus and then exposed to cigarette smoke daily for 36 weeks, they were able to mount a secondary immune response of normal height on subsequent challenge with the homologous virus strain. The response however, was less specific than that elicited in control mice, with high titres of cross-reacting antibody by haemagglutination-inhibition to the following strain in the same antigenic series. Recall of antibody to the previous strain in the antigenic series was not observed in either control or smoke-exposed animals. These results serve to correct an earlier discrepancy between the murine system and human studies in which the response to influenza infection in mice was depressed by prolonged exposure to cigarette smoke, whereas in man the response of smokers did not differ significantly from that of non-smokers. This apparent discrepancy had been caused by a lack of previous experience of influenza in the mice, which had therefore mounted a primary response, compared with the secondary response observed in the human studies.     

孕鼠香烟烟雾染毒对胎鼠视杯和视泡上皮细胞凋亡的影响

[目的]观察孕鼠香烟烟雾染毒致胎鼠眼畸形的作用及对视杯、视泡上皮细胞和问充质细胞凋亡的影响.[方法]将怀孕的金黄地鼠随机分为吸烟组和对照组,吸烟组共3组(每组10只动物)分别于孕第6、7、8天开始用香烟烟雾染毒(即A、B、C组);对照组(共15只动物)除无烟熏外,其他条件同吸烟组.分别于染毒第3天时,在体视显微镜和光镜下观察各组鼠胚的发育情况及眼畸形的形态学变化;采用原位末端标记法定量分析金黄地鼠胎鼠视杯、视泡上皮细胞及间充质细胞凋亡的变化.[结果]孕鼠香烟烟雾染毒对胚胎有显著致畸作用,吸烟组总畸形率为40.08%,眼畸形率为10.32%,与对照组相比差异均有统计学意义(P<0.01),其中以孕7天开始染毒组畸形率最高(51.69%).吸烟组视杯、视泡上皮细胞及间充质细胞的凋亡细胞数明显高于对照组(P<0.05),且以孕7天开始染毒组凋亡细胞计数最高,为(29.1±2.1)个.组织学观察发现,吸烟组胎鼠视杯的发生明显迟干对照组.[结论]香烟烟雾染毒对胚胎有明显眼致畸作用;香烟烟雾可以诱导视杯、视泡上皮细胞及间充质细胞过度凋亡,导致视杯的发生明显延迟,这可能是香烟烟雾染毒致胚胎眼畸形发生的机制之一.     

Pulmonary tissue and cigarette smoke: 2. Parenchymal response

Cigarette smoke and hydrocortisone acetate (HCA) induce marked abnormalities in lungs of $\text{C57BL}\text{6}\text{J}$ male mice. In many pulmonary regions of smoke-exposed, HCA-treated animals, alveoli were highly congested with surfactant and flocculent material. In addition, prominent alveolar collapse and septal hypertrophy were common. These conditions resembled pulmonary alveolar proteinosis described in humans. Administration of HCA to sham-treated animals also produced lung abnormalities, however, considerably milder in severity, while stress (resulting from sham treatment) or HCA injections of mice alone failed to induce any pulmonary tissue disorder. Data reported indicate that the genesis of abnormal conditions which resemble pulmonary alveolar proteinosis is potentiated by cumulative effects of different treatments (i.e., smoke, HCA, and stress), most significant being the interaction between cigarette smoke and the steroid.