Tumors Of Respiratory Tract Research Articles

Induction of respiratory tract tumors in Syrian golden hamsters by a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the effect of smoke inhalation.

Four groups of 10 male and 10 female Syrian golden hamsters were given single s.c. injections of either 0.3 ml of trioctanoin or of 0.3 ml of trioctanoin containing either 1.0 mg, 3.3 mg, or 10.0 mg of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These hamsters were then exposed to cigarette smoke for the next 72 weeks. Four control groups received the same injections of NNK or trioctanoin but were treated by sham smoking. All groups treated with NNK had tumors of either the lung, nasal mucosa, and/or trachea. These tumors were not observed in hamsters injected with trioctanoin. These results demonstrate that even a single dose of NNK can induce respiratory tract tumors in Syrian golden hamsters. Smoke inhalation did not result in an increase in respiratory tract tumor incidence in most of the NNK treated groups.

Intratracheal instillation of automobile exhaust condensate in Syrian golden hamsters.

Male Syrian golden hamsters were intratracheally instilled with automobile exhaust condensate at dose levels of 0.306, 0.613, 1.25, 2.5, and 5.0 mg/hamster once a fortnight for 78 weeks. While a total of six tumors were found in the trachea and lung, hamsters treated with the vehicle only showed no respiratory tract neoplasms. Bronchiogenic adenomatous proliferations and hyperplastic nodules in the lung occurred in all groups, with a significant difference in incidence being seen between the high-dose groups and the controls.

Tumors of the Lower Respiratory Tract

Tumors of the Lower Respiratory Tract

Respiratory tract tumours in hamsters exposed to acetaldehyde vapour alone or simultaneously to benzo(a)pyrene or diethylnitrosamine

Syrian golden hamsters were exposed to 0 or 2500–1650 ppm acetaldehyde vapour, 7 hr/day, 5 days/week for a period of 52 weeks. A proportion of the animals was given, simultaneously, either intratracheal instillations of benzo(a) pyrene (BP) or subcutaneous injections of diethylnitrosamine (DENA). All treatments were stopped after 52 weeks. The study was terminated after 81 weeks. Major effects attributed to acetaldehyde exposure included growth retardation, rhinitis, hyperplasia and metaplasia of the nasal, laryngeal and tracheal epithelium, nasal and laryngeal carcinomas, and a markedly increased incidence of BP-initiated tracheobronchial carcinomas. There was no evidence of acetaldehyde enhancing the development of DENA-initiated tumours of the respiratory tract. It was concluded that acetaldehyde is an irritant, as well as a carcinogen, for the respiratory tract of Syrian golden hamsters. Possible mechanisms of the carcinogenicity of this aldehyde are briefly discussed.

Tumors of the Lower Respiratory Tract

Tumors of the Lower Respiratory Tract

Tumors of the Lower Respiratory Tract.

Remarkable advances have occurred since the Series 3 Fascicle published in 1995 with paradigm shifts in every dimension of our understanding of lung tumors including clinical, radiologic, histopathologic, cytopathologic, immunohistochemical, molecular and therapeutic aspects. The molecular revolution leading to effective targeted therapies and breakthroughs in immunotherapy for lung cancer have led to novel approaches incorporating the concept of personalized medicine for patients who historically had little hope. These advances have strengthened the place of pathologists to play a central role in the multidisciplinary team that is now needed to properly diagnose and manage lung cancer patients.

Second primary respiratory tract malignant neoplasms in supraglottic carcinoma.

In this study, a second respiratory tract malignant neoplasm developed in 20 of 163 cases of supraglottic carcinoma either at the time of diagnosis or after diagnosis. Using an actuarial method of calculation, 19% of the survivors will experience a second respiratory tract malignant neoplasm within five years after the diagnosis of supraglottic carcinoma. This is three times the incidence in patients who survive glottic carcinoma and 14 times the incidence in the normal population. A third of this group of patients with supraglottic carcinoma are alive and well at five years, a third died of supraglottic cancer, and a third died of intercurrent disease. The death rate from intercurrent disease is twice that seen in the general population, and this difference is due almost entirely to second respiratory tract tumors. Even if the cure rate of patients with primary supraglottic carcinoma was 100%, only half of these patients would actually be alive at five years, owing to deaths from intercurrent disease. More emphasis needs to be placed on the reduction of the mortality from second respiratory tract tumors with the use of screening or preventive methods.

The metabolism of 7 H-dibenzo[ c,g]carbazole, an N-heterocyclic aromatic, in the isolated perfused lung

The metabolism of a carcinogenic N-heterocyclic aromatic, 7 H-dibenzo[ c,g]carbazole, was investigated in an isolated perfused rabbit lung preparation and in rat liver microsomes. A major metabolite produced in both preparations is the 7-hydroxydibenzo[ c,g]carbazole. A substantial percentage of this metabolite is found in the tracheabronchi, which would be consistent with the high incidence of respiratory tract tumors due to dibenzo[ c,g]carbazole.

Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats.

Inhalation exposure experiments with the direct-acting alkylating agent epichlorohydrin (ECH) were done on noninbred male Sprague-Dawley rats. Single 6-hour exposure to ECH and follow-up for 14 days showed the median lethal concentration to be about 360 ppm. Further inhalation experiments were done with 6-hour exposure 5 days/week. A short-term 30-exposure regimen with 100 ppm ECH produced malignant squamous cell carcinomas of the nasal cavity in 15 of 140 rats and respiratory tract papillomas in 3 rats. Among 100 rats, lifetime exposure to 30 ppm yielded 1 malignant squamous carcinoma of the nasal cavity plus 1 nasal papilloma. No nasal or respiratory tract tumors were produced by lifetime exposure of 100 rats to 10 ppm. As controls, 100 air-treated and 50 untreated rats were used. A dose-rate effect was observed for ECH inasmuch as 30-day exposure to 100 ppm (3,000 ppm-days) produced 15 cancers in comparison to the 1 cancer from the lifetime exposure to 30 ppm (8,700 ppm-days) and no cancers from lifetime exposure to 10 ppm (2,500 ppm-days).

Significance of particle size of benzo(a)pyrene for the induction of respiratory tract tumours in hamsters.

To study the role of particle size of benzo(a)pyrene (BP) in the induction of respiratory tract tumours, goups of hamsters were given 52 weekly intratracheal instillation of fine (77% less than 5.2 micron; 3% less than 1.3 micron) or coarse (77 less than 42 micron; 0% less than 10 micron) BP particles suspended in gelatin-0.9% NaCl solution. Both the fine and coarse particles were given at two different dose levels, viz., 0.5 and 1.0 mg BP/instillation. Another group of hamsters received 52 weekly intratracheal instillations each consisting of 1.0 mg BP particles of a wide size range (90% less than 50 micron; 3% less than 5.0 micron) suspended in 0.9% NaCl solution without gelatin. The retention of BP in the respiratory tract was studied in separate groups of hamsters receiving a single instillation of BP particles of the different size ranges. Coarse BP particles cleared less rapidly from the lungs and induced a much stronger tumour response in the respiratory tract than did fine BP particles. These findings demonstrated the crucial significantce of particle size for the effectiveness of BP as a respiratory tract carcinogen. No appreciable differences in site of tumour formation were observed between treatment with fine and coarse BP particles, which led to the conclusion that the size of the particles did not play an important role in determining the location of the induced respiratroy tract tumours. The elimination rate of the BP particles with a wide size range appeared to be in between those of the fine and the coarse particles. The tumour response found after administration of the BP particles of wide size range was very similar to that obtained with the high dose of coarse PB particles.

Failure of two retinoids to inhibit tracheal carcinogenesis in hamsters

The effect of 2 retinoids, 13-cis-retinoic acid and 4-methoxy-2,3,6-trimethylphenyl analog of retinoic acid ethyl amide (designated Roll-1430), on tracheal tumor development in hamsters exposed to N-nitroso-N-methylurea was tested. Hamsters were intratracheally exposed either 18, 20, or 23 times to 1% N-nitroso-N-methylurea before the retinoids were administered in the diet. Evidence was presented which indicates that the great majority of the animals are free of invasive neoplasia at the start of retinoid feeding. In none of the 6 retinoid-treated groups could a statistically significant inhibition of tumor development be demonstrated. Hamsters treated with 13-cis-retinoic acid (128 or 172 mg/kg of diet) tended to have an elevated cancer risk; this effect was at a statistically significant level in the group treated with 172 mg/kg of diet. The distribution of histologic tumor types seemed to be shifted in favor of adeno and mixed adeno-epidermoid tumors in the group receiving a low carcinogen dose and Roll-1430. Similar to earlier studies with retinyl acetate tested in hamsters and rats, 13-cis retinoic acid and the retinoic acid ethyl amide analog Roll-1430, failed to inhibit development of respiratory tract neoplasms. We suspect that the reason for this is the absence of significant promoting influences in the current lung cancer models and that retinoids act mostly as anti-promoters.

Book reviews

Book reviewed in this article:International Histological Classi3cation of Tumours, No. 19. Histological Typing of Upper Respiratory Tract Tumours Edited by K. Shanmugaratnam, L. H. Sobin and othersInternational Histological Classification of Tumours, No. 20; Histological Typing of Tumours of the Liver, Biliary Tree andpancreas Edited by J. B. Gibson and others.The Pathology of Violent Injury Edited by J.K. Mason.

Histological Typing of Upper Respiratory Tract Tumours (International Histological Classification of Tumours, No. 19)

Histological Typing of Upper Respiratory Tract Tumours (International Histological Classification of Tumours, No. 19)

Investigations on the carcinogenic burden by air pollution in man. Intratracheal instillation studies with benzo[ a]pyrene in a mixture of Tris buffer and saline in Syrian golden hamsters

Syrian golden hamster received intratracheal instillations of 0.125, 0.25, 0.50 or 1.0 mg benzo[a]pyrene (B[A]P) in a mixture of Tris buffer and physiological saline once weekly for life. Papillary polyps, squamous cell papillomas and carcinomas developed in both the larynx and trachea. In addition, bronchiogenic adenomas, adenocarcinomas and squamous cell carcinomas were induced in the lung. The highest incidence of respiratory tract tumours (83%) was seen in hamsters receiving 0.25 mg B[a]P. The results of these investigations are statistically evaluated and discussed.

Experimental Respiratory Carcinogenesis in Hamsters: Environmental, Physicochemical and Biological Aspects

The respiratory tract of Syrian golden hamsters was exposed to polycyclic hydrocarbons alone and in combination with dusts. These included benzo(a)pyrene (B(a)P), silicon dioxide (SiO₂), manganese dioxide (MnO₂) and agar gelatin (gel), as well as dibenz(a, j)acridine (DBA) in combination with the carrier dust ferric oxide (Fe₂O₃). The purpose of the study was to evaluate the possible environmental hazards of these compounds and the physicochemical characteristics determining their carcinogenic activity. We also wished to study the prognostic significance of premalignant alterations in relation to treatment by carcinogenic and noncarcinogenic agents and the applicability of respiratory tumor classification in this system. When instilled alone, the dusts induced bronchial nonspecific epithelial alterations, interstitial cell proliferation and a few granulomatous changes in the lung. No respiratory tract tumors were seen. B(a)P alone induced only tracheal epithelial alterations, desquamation and metaplasia, as well as five papillomas and one squamous cell carcinoma. B(a)P in a suspension of gelatin-saline induced a few papillomas and squamous cell carcinomas of the trachea and lungs. SiO₂ with B(a)P was highly effective and induced papillomas, squamous cell carcinomas, adenomas and adenocarcinomas of the larynx, trachea and lungs. They were preceded by epithelial proliferative dysplastic alterations, not seen in animals treated with B(a)P and MnO₂ or DBA and Fe₂O₃. These groups also failed to exhibit a significant neoplastic response. The tumors could be divided into benign and malignant, glandular or squamous cell tumors. The trachea, main bronchi, bronchioli and lungs showed the efficacy and applicability of a classification similar to that used in man. It is also concluded that preneoplastic alterations sufficient in degree and extent are indicative of subsequent tumor formation.

Bronchoplastic procedures in the treatment of carcinoid tumors of the tracheobronchial tree

Sixteen patients, aged 10 to 70 years, had carcinoid tumors of the lower respiratory tract treated by various resective tracheobronchoplastic procedures. These represent 8.8 percent of 181 patients with carcinoid lesions treated during a recent 20 year period. All 16 patients had respiratory symptoms, and one patient also had the carcinoid syndrome. Roentgenographic changes ranged from a mass or atelectasis (or both) through unilateral lung hyperinflation to clear lungs with subtle filling defects in major airways. All tumors were visualized endoscopically, and 13 patients had biopsies. Histopathologically, all tumors were "typical" carcinoids . Before operation, the patients had minimal or no respiratory insufficiency, although flow-volume and ventilation-perfusion abnormalities were noted when major airways were affected. Surgical management at thoracotomy was as follows: (1) simple wedge tracheobronchotomy without lung resection (five patients); (2) bronchial sleeve resection without lung resection (three patients); and (3) bronchial sleeve with upper lobe resection (eight patients). These 16 operations were performed with eight technical anatomic variations. No early or late deaths occurred. One patient had early transient atelectasis, and three patients required late endoscopic removal of suture granulation tissue. All patients were alive without recurrence of tumor or carcinoid syndrome or other respiratory complications 6 months to 19 years postoperatively. Pulmonary resection should be avoided unless there is histologic evidence of tumor extension into lung parenchyma or irreversible pulmonary suppuration distal to the obstructive tumor.

Role of particle size in the formation of respiratory tract tumors induced by benzo(a)pyrene

The role of particle size in experimental respiratory tumor formation was studied by intratracheal instillation of two different particle sizes of benzo(a)pyrene into Syrian golden hamsters. One group of hamsters received large particles ( 64% above 10 μ m), the second group was treated with smaller-sized particles ( 98% less than 10 μ m). Otherwise, treatment was similar. Only 5 respiratory tumor-bearing animals of 48 were found in the group receiving small particles, whereas 31 respiratory tumor-bearing animals of 48 were found in the group which received the larger particles. Analysis of the retention rate of instilled B(a)P showed that small particles cleared much more rapidly from the lungs than did the larger particles.

Investigations on the carcinogenic burden by air pollution in man. Intratracheal instillation studies with benzo(a)pyrene in bovine serum albumin in syrian hamsters

The chronic effect of benzo(a)pyrene (B(a)P) administered intratracheally in bovine serum albumin was studied in Syrian golden hamsters. Dose levels of 0.1 mg, 0.33 mg and 1.0 mg of B(a)P induced papillomas and carcinomas of the trachea, stem bronchi and bronchioles. In addition to such tumours, the mucosa of the respiratory tract revealed a variety of atypical epithelial alterations. Although survival time exhibited a dose-dependency, tumour incidence did not. The incidence of respiratory tract tumours was higher in female hamsters than in males. The results of these investigations are statistically evaluated.

Tumur induction by 7H-dibenzol[c,g] carbazole in the respiratory tract of Syrian hamsters.

The respiratory tract of male and female Syrian golden hamsters was treated intratracheally with 7H-dibenzo[c,g]carbazole (DBC), a tobacco smoke component. The carcinogen was given by multiple instillations at two dose levels. At the lower dose (9 mg), 35 of 46 hamsters (72%) developed respiratory tract tumors. The group receiving treatment at the higher dose level (30 mg) died earlier because of the toxicity of the compound. In this group, 15 of 45 animals (33%) had respiratory tract tumors. These occurred in the larynx, trachea, bronchi, and lungs, but predominated in the trachea and bronchi. Morphologically, most tumors were papillomas and squamous cell carcinomas. This study indicates the highly potent carcinogenic effect of DBC and that respiratory tumors can be induced in this model system without any carrier dust.

Diallylnitrosamine: A Potent Respiratory Carcinogen in Syrian Golden Hamsters: Brief Communication2

Diallylnitrosamine (DAN), one of the few nitrosamines tested thus far that has not induced neoplasms in rats, caused a high incidence of respiratory tract tumors in Syrian golden hamsters treated sc with single or weekly doses of the compound. The effect was dose-dependent. The nasal cavity, larynx, and trachea were the most affected by DAN; most drug-induced tumors at those sites were adenocarcinomas and papillary polyps.