Tract Tumors In Hamsters Research Articles

Modulation of N-Nitrosodiethylamine Induced Hamster Lung Tumors by Nitrogen Dioxide

AbstractThe objective of the study was to examine whether continuous exposure to NO2 would modify the development of chemically induced lung tumors. Male Syrian golden hamsters were treated, twice a week, with sc injections of N-nitrosodiethylamine (DEN) while being exposed for 23 h/d, 7 dlwk to 15 ppm of NO2. Animals were sacrificed 4 mo and 6–8 mo after the beginning of the experiment. No lung tumors were found in hamsters treated with DEN and exposed to NO2 whereas 26% of the animals treated with DEN alone had peripheral lung tumors after 6–8 mo. The development of tracheal tumors was delayed by exposure to the pollutant. The results of the experiment do not allow implication of NO2 as a possible enhancer of respiratory tract tumors in hamsters.

The effect of beta-carotene on BP-induced respiratory tract tumors in hamsters.

The modifying effect of beta-carotene on benzo[a]pyrene (BP)-induced tumors of the respiratory tract was investigated in Syrian hamsters. Groups of hamsters were fed a semisynthetic diet supplemented with either no or 56 mg/kg beta-carotene. Respiratory tract tumors were induced by intratracheal instillation of BP attached to ferric oxide. The beta-carotene and vitamin A contents of the liver were increased in the high beta-carotene group, but the serum beta-carotene levels were very low when compared with those commonly observed in humans. beta-Carotene supplementation did not affect the tumor response of the respiratory tract. Neither the incidence and severity of preneoplastic changes were influenced. However, there was a statistically significant inverse relationship between serum retinol content and the presence of respiratory tract tumors in survivors, regardless of the dietary treatment.

Dietary selenium- and benzo[a]pyrene-induced respiratory tract tumours in hamsters.

The modifying effect of selenium as sodium selenite on chemically induced respiratory tract tumours was tested in Syrian golden hamsters. Groups of 40 hamsters per sex (controls 60 per sex) were fed the following semisynthetic diets: control diet (0.1 p.p.m. Se, low fat); high-Se diet (5 p.p.m.); high-fat diet (20% sunflower oil); or high-Se + high-fat diet. After an adaptation period of 30 days on the diets, respiratory tract tumours were induced by intratracheal instillation of benzo[a]pyrene attached to ferric oxide. The experimental period was 429 days for males and 374 days for females. Respiratory tract tumours included mainly epidermoid papillomas, epidermoid carcinomas and combined epidermoid and adenocarcinomas. Selenium included either in a low-fat or high-fat diet did not influence the tumour response in the respiratory tract or in other organs. Neither was there a correlation between the serum or liver Se levels in the presence of respiratory tract tumours. The tumour response in the respiratory tract and also in other organs was slightly respiratory tract and also in other organs was slightly enhanced by dietary fat.

Respiratory tract tumors in hamsters after severe focal injury to the trachea and intratracheal instillation of benzo[ a]pyrene

Two groups of male and female Syrian golden hamsters, of which the trachea was severely injured by electrocoagulation, received 6 weekly intratracheal instillations of benzo[ a]pyrene (BaP) + ferric oxide in saline or saline alone. Two comparable groups of hamsters were similarly treated but had an undamaged trachea. The experiment was terminated in week 82. Treatment with BaP resulted in hyper- and metaplastic lesions and tumours of the laryngeal, tracheal, bronchial and pulmonary epithelium. There was no evidence of an increased incidence of BaP-induced tumours in the injured trachea.

DNA ethylation in target and non-target organs of hamsters and rats treated with diethylnitrosamine

Kinetics of ethylation of target and non-target organ DNA in vivo by diethylnitrosamine (DEN) was compared in rats and Syrian golden hamsters, since published reports indicate a single dose of DEN induces both kidney and liver tumors in rats and almost exclusively respiratory tract tumors in hamsters. Following treatment with 200 mg DEN/kg, 7-ethylguanine (7-etG) was lost more rapidly from hamster than from rat liver DNA, while O 6 -ethylguanine (O 6 -etG) persisted longer in hamster than in rat liver DNA. DNA ethylation was not detected in rat lung (non-target organ), while both 7-etG and O 6 -etG were quantitated in hamster lung (target organ) following DEN treatment. DNA ethylation in rat kidney DNA was ∼ 1 10 of that in liver by 200 mg DEN/kg, and the persistence of 7 -etG and O 6 -etG differed only slightly in these tissues. Ethylation of hamster liver DNA by DEN at doses between 20 and 200 mg/kg, as measured by 7 -etG and O 6 -etG was proportional to the dose of carcinogen up to 160 mg/kg; at larger doses DNA ethylation sharply increased. Differences in the persistence of O 6 -etG between DEN-treated rats and hamsters cannot solely account for species differences in the organotropism of DEN carcinogenesis.

Modifying effect of dietary fat on benzo[a]pyrene-induced respiratory tract tumours in hamsters.

Groups of 40 Syrian golden hamsters of both sexes were fed diets containing either 5% fat (control), 20% saturated fat (beef tallow) or 20% unsaturated fat (sunflower seed oil) from weaning and during the whole experimental period (up to 656 days). Respiratory tract tumours were induced by intratracheal instillation of benzo[a]pyrene attached to ferric oxide and suspended in saline. Mortality was slightly, but not statistically significantly higher in the high fat groups than in the low fat control group. Microscopic examination of the respiratory tract revealed an increased number of tumour bearing animals, an increased multiplicity of respiratory tract tumours and an increased total number of respiratory tract tumours in animals fed high fat diets. The tumour enhancing effect of fat was most pronounced in the high unsaturated fat group. Especially epidermoid papillomas, epidermoid carcinomas and combined epidermoid and adenocarcinomas contributed to the observed differences in tumour response amongst groups. It was concluded that dietary fat enhances benzo[a]pyrene-induced respiratory tract carcinogenesis in hamsters.

Modifying effect of vitamin A on benzo[a]pyrene-induced respiratory tract tumours in hamsters.

Groups of 40 hamsters of each sex were fed natural ingredient diets containing 600, 4000 or 100 000 IU vitamin A/kg. After an adaptation period of 170 days on the diets, respiratory tract tumours were induced by intratracheal instillation of benzo[a]pyrene + ferric oxide suspended in saline. Mortality was statistically significantly increased in the high dose group as compared with the mid (control) and low dose group. Microscopy of the respiratory tract did not reveal any significant differences in tumour response between the various dose groups. However, the incidence of preneoplastic respiratory tract lesions was distinctly inversely correlated with the oral vitamin A dose. The serum retinol values were similar in the various dose groups, without any indication of a dose related increase. It was concluded that under the experimental conditions used vitamin A did not influence benzo[a]pyrene-induced respiratory tract cancer in hamsters.

Comparative carcinogenicity in F344 rats and Syrian golden hamsters of N′-nitrosonornicotine and N′-nitrosonornicotine-1- N-oxide

N′-Nitrosonornicotine (NNN) or N′-nitrosonornicotine-1- N-oxide (NNN-1-N-oxide), one of its metabolites, was added to the drinking water (0.012% for 36 weeks) of groups of male and female F344 rats or to the drinking water (0.016% for 31 weeks) of groups of male and female Syrian golden hamsters. All rats treated with NNN had died after 12 months but 50% of those treated with NNN-1-N-oxide survived for 22 months. NNN induced esophageal tumors in 23 24 rats and nasal cavity tumors in 21 24 rats. NNN-1-N-oxide induced esophageal tumors in 10 24 rats and nasal cavity tumors in 18 24 rats. There was no difference in survival rates among hamsters treated with either NNN or NNN-1-N-oxide. NNN induced tracheal tumors in 2 20 hamsters and nasal cavity tumors in 4 20 hamsters. NNN-1-N-oxide did not induce respiratory tract tumors in hamsters. These results demonstrate that NNN-1-N-oxide is less carcinogenic than NNN in F344 rats and Syrian golden hamsters.

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.

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.