N-nitrosodimethylamine and 7-methylguanine DNA adducts in tissues of rats fed Chinese salted fish.

Previous studies have demonstrated that rats fed Chinese salted fish developed carcinomas of the nasopharynx and nasal cavity. In the present work the contents of nitrosamines in salted fish from the city of Guangzhou, southern China, and the contents of nitrosamines and possible nitrosamine-induced DNA adducts in organs of rats fed the fish were analysed. Similar levels of N-nitrosodimethylamine (NDMA) were detected in tough and soft salted fish. The NDMA content in steamed fish was higher than in raw fish. In vitro incubation of salted fish with gastric juice significantly increased the level of NDMA. NDMA was found in liver and kidney from rats fed salted fish for 2 years, but no dose-dependence was found between salted fish treatment and NDMA content. The level of 7-methylguanine in rat liver DNA was found to be slightly higher than in DNA from nasopharynx. However, there were no significant differences in the level of 7-methylguanine in DNA samples from rats fed salted fish and rats fed standard diet.

Basic experimental studies of ostial patency and local metabolic environment of the maxillary sinus.

Experimental studies of human maxillary sinus gas exchange show that there is a balance between inflow of air through the maxillary ostium and local consumption as long as the functional size of the ostium is at least 5 mm2. Maxillary sinus mucosal blood flow is 30-40 ml/100 g tissue per minute, as measured in plethysmographic studies. This blood flow can bind and transport only half of the absorbed oxygen, the rest is consumed. Experimental histo- and biochemical studies of sinusitis show anaerobic mucosal metabolism with shortage of energy supply due to inadequate oxygen supply. There is no decrease in oxidative enzyme capacity of the mucosal epithelium. Analysis of organic acids in purulent secretion indicates that the high lactate and CO2 concentration found is mainly the result of leucocyte glycolysis with local lactic acidosis. Both ostial occlusion and the initiation of bacterial growth in serous sinusitis may be secondary to an initial inflammatory response, resulting in local tissue pathology and swelling of the ostiomeatal complex, as well as creating the appropriate redox potential for further bacterial growth in the secretions.

Epstein-Barr virus infection, salted fish and nasopharyngeal carcinoma. A case-control study in southern China.

Two hundred and five histologically confirmed cases of nasopharyngeal carcinoma (NPC) in southern China, and an equal number of matched controls, were investigated for their dietary habits, occupational exposure, use of tobacco and alcohol, history of relatives with NPC, and IgA against Epstein-Barr virus (EBV) capsid antigen (IgA/VCA). Positive IgA/VCA and intake of salted fish were associated with a strong excess risk of NPC. The association persisted after adjustment for other factors. The combination of salted fish and EBV was strongly associated with NPC, and more so than EBV or salted fish per se. Multivariate analyses showed that IgA/VCA was the most important predictor of NPC, and salted fish the second most important. These results suggest that EBV has a strong effect on the development of NPC. The exclusion of EBV and genetic factors in earlier epidemiological studies may have resulted in an overestimation of salted fish as important etiological factor causing NPC.

Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with Chinese salted fish.

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on etiological factors of nasopharyngeal carcinoma.

A case-control study of nasopharyngeal carcinoma (NPC) was performed in Guangzhou, southern China in 1987 to 1989. We investigated 205 cases and an equal number of matched controls. Epstein-Barr virus (EBV) infection with positive IgA against viral capsid antigen (VCA-IgA) was shown to be the most important predictor in NPC. Consumption of salted fish was also strongly associated with NPC but not to the same extent as EBV. In order to investigate the possible carcinogenic effect of salted fish, Sprague-Dawley rats were given a diet containing salted fish for 2 years. Three rats with nasal and 3 with nasopharyngeal tumors were found in the experimental groups of 122 rats but none in the control group. Nitrosodimethylamine (NDMA) was found in kidney and liver but not in urine in the rats fed with salted fish. In a non-tumorigenic human keratinocyte line, RHEK-1, transfection of EBV latent membrane protein (EBV-LMP, originated from NPC cell line) induced alterations of morphology and immunophenotype. The LMP expressing sublines showed higher proliferative capacity and lower differentiation in vitro and some of the sublines produced tumors in SCID mice. When cultured in media containing salted fish extract in vitro parental RHEK-1 cells died after 12 weeks. In contrast, LMP expressing sublines survived indicating that exposure to some chemical compounds in salted fish and expression of EBV-gene may be of importance for the transformation of epithelial cells and thus for the pathogenesis of NPC.

Epidemiological studies of nasopharyngeal cancer in the Guangzhou area, China. Preliminary report.

In the city of Guangzhou (Canton) and its surroundings nasopharyngeal cancer (NPC) constitutes about 32% of all cancer and is therefore the most common kind of cancer. Three types of etiological factors seem to be involved: 1) a hereditary factor, 2) Epstein-Barr virus, and 3) external factors in food and water. An epidemiological study has been started in the Guangzhou area with interviews of NPC cases, matching controls and mothers of the cases and controls concerning especially food and environmental factors and infections in childhood. The questions put to the controls and cases covered the last seven years and the age of ten, while those to the mothers covered the first three years of life and the age of ten for the controls and cases. Results are now available for 140 cases, 140 controls and the corresponding living mothers. They indicate that salted fish, particularly of Cantonese style, was consumed more by NPC cases than by controls and also had more frequently been given to weaning children in whom NPC later developed. Furthermore, salted vegetables and salted pork were consumed to a greater extent by NPC cases than by controls. Drinking of polluted water in childhood was more common among the NPC cases. Consumption of fresh fruit was more rare among the cases. Most of the NPC cases had a positive VCA-IgA titre.

Experimentally induced sinusitis: the importance of vasomotor regulation.

An acute pneumococcal maxillary sinusitis was induced in New Zealand white rabbits by unilateral obstruction of the sinus ostium and then injecting 10(8) Streptococcus pneumoniae into the sinus. After subjecting this bacterial strain to one animal passage, the bacteria were reisolated in nine of ten infected maxillary sinuses. All rabbits developed a unilateral purulent sinusitis, while a non-purulent sinusitis could be induced by occlusion only of the maxillary ostium. By using a non-diffusable tracer, microspheres labelled with Sn113, blood flow measurements were performed on these sinuses. These studies showed that the blood flow of the infected sinuses was significantly higher than on the control side. However, in chronic sinusitis (with a blocked ostium), the blood flow did not differ significantly from that on the control side. Biochemical studies in the animals with purulent sinusitis demonstrated that lactate concentration in the mucosa was significantly higher as compared to the control side. The glucose concentration was significantly lower in the mucosa of the infected side, as was the ATP content of the sinus mucosa in purulent sinusitis. These results indicate an increased glycolysis as well as a relative energy depletion in the sinus mucosa in purulent sinusitis, which could result in an impaired epithelial function.

Experimental acute sinusitis in rabbits. A bacteriological and histological study.

A bacteriological and histological study of experimentally induced acute pneumococcal sinusitis was performed in 69 New Zealand White rabbits. The sinus ostium was blocked on one side on the first day of the experiment. On the second day, 10(7)-10(9) Streptococcus pneumoniae in 1 ml were injected into the same sinus cavity. Purulent sinusitis developed unilaterally in all rabbits. Histological examination of the sinus mucosa revealed edema, dilated venules, leukocytic infiltration of the mucosa as well as localized epithelial lesions. On staining with acridine orange at pH 4.0, the bacteria were observed in the secretion but not in the mucosa. When we used Streptococcus pneumoniae subjected to an animal passage, the bacteria were re-isolated in 9/10 infected sinuses. Neither sole occlusion of the ostium nor injection of pneumococci into a sinus cavity with a patent ostium resulted in a bacterial sinusitis. Obstruction of the sinus ostium and the use of a virulent Streptococcus pneumoniae strain were essential for the induction of sinusitis in rabbits.

Therapeutical aspects of sinusitis in relation to pathogenesis.

Modern aspects of the pathophysiology of sinusitis have given further evidence of the importance of ventilation and drainage as therapeutical procedures. A simple therapeutical method for implantation of a tube in the maxillary sinus for treatment of acute sinusitis is presented.

Experimental acute sinusitis in rabbit. A study of mucosal blood flow.

An experimental model of sinusitis in the rabbit was developed, using type 3 pneumococci. The superior parts of the rabbit maxillary sinuses were surgically exposed and the maxillary ostium was unilaterally blocked. The following day a challenge dose of 10(7)-10(9) colony-forming units of Streptococcus pneumoniae, capsular type 3, was injected into the sinus. When the pneumococci used had been subjected to an animal passage, bacteria were recultured after 4 days. Histological examination showed thickening of the mucosa, with dilated venules and infiltration of granulocytes. No bacteria were seen in the mucosa on staining with acridine orange. With use of microspheres 15 micron in diameter labelled with Sn113, the mucosal blood flow was found to be higher than on the control side.

The effect of ipratropium bromide (Atrovent) on the air conditioning capacity of the nose.

The air conditioning capacity of the nose was assessed by a method which permits measurements in both nasal cavities without blockage of the passage between the nasopharynx and oropharynx. By this method the degree of warming of the air and its humidification during the passage through the nasal cavity can be calculated. The effect of intranasal application of ipratropium bromide (Atrovent) on the air conditioning capacity of the nasal mucosa was evaluated in a group of normal subjects and a group of patients with vasomotor rhinitis. In this short term trial Atrovent was found not to have any effect on this capacity.

Experimental studies on carcinogenesis in the nasal mucosa.

Of 24 Syrian golden hamsters exposed to wood dust in a concentration in the air of 30 mg/m3 for 6 h per day, 5 days a week, for a period of 40 weeks, one animal got dysplasia and one a malignant tumour in the nasal mucosa. In a group of 24 animals given 3 mg of diethylnitrosamine subcutaneously once a week for 12 weeks, a high frequency of benign and malignant tumours (mainly adenocarcinoma) of the nasal mucosa was found, but a group of similar size exposed to both wood dust and diethylnitrosamine did not show a higher frequency of nasal tumours than those given this latter substance alone.

Blood flow in the rabbit maxillary sinus mucosa. Measurement with a diffusible and a non-diffusible tracer.

The blood flow of the sinus mucosa was studied in 11 New Zealand White rabbits. Their body weight averaged 3.5 kg. The blood flow determinations were performed during neurolept anaesthesia with continuous blood pressure recording. The blood flow in the sinus mucosa and septum, as well as in other organs, was determined both with Sn113-labelled microspheres and with Rb86Cl. Cardiac output as determined with the microsphere method was 146 +/- 36 ml X min-1 X 1000 g-1 body weight. There was a good correlation between the blood flow values obtained with the two methods. The blood flow in the sinus mucosa was 0.58 +/- 0.41 ml X min-1 X g-1 when measured with microspheres and 0.43 +/- 0.34 ml X min-1 X g-1 with the Rb86Cl technique. In the septal mucosa the corresponding values were 0.42 +/- 0.20 ml X min-1 X g-1 and 0.49 +/- 0.43 ml X min-1 X g-1 respectively.

Effects of wood dust exposure and diethylnitrosamine. A pilot study in Syrian golden hamsters.

Fine wood dust is epidemiologically associated with human nasal cancer. The aim of the present study was to elaborate an animal model for inhalation studies of the effects of fine wood dust on the upper and lower airways. Syrian golden hamsters were used. After 10 months one animal in the group which was exposed only to wood dust, had developed a malignant nasal tumour and another animal in the same group had nasal dysplasia. Spontaneous nasal tumours in this laboratory animal is not known. Many tumours of the nose, larynx and trachea arose in animals treated with a carcinogen (diethylnitrosamine). There was no increase in tumours in animals with combined exposure to diethylnitrosamine and wood dust.