Carcinogenic and cocarcinogenic effects of radon and radon daughters in rats.

It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures.

Mortality of a cohort of French uranium miners exposed to relatively low radon concentrations.

A cohort mortality study has been performed on French uranium miners having experienced more than 2 years of underground mining, with first radon exposure between 1946 and 1972. Vital status has been ascertained from the date of entry to the 31 December 1985 for 99% of the members of this cohort; causes of death are identified for 95.5% of the decedents. The different causes of death are compared to the age specific national death rates by indirect standardisation and expressed by standardised mortality ratios (SMR). A statistically significant excess has been observed for lung and laryngeal cancer deaths. The Poisson trend test shows a statistically significant trend for the risk of lung cancer death as a function of cumulative radon exposure, assuming a lag time of 5 years; for laryngeal cancer no significant trend has been observed. Poisson regression modelling has been applied to the following exposure groups: < 10 WLM (Working Level Month); 10-49 WLM; 50-149 WLM; 150-299 WLM; > or = 300 WLM; it indicates an increase in the SMR for lung cancer of 0.6% per WLM (standard error: 0.4%) with an estimated intercept at 0 WLM of 1.68 (standard error: 0.4). The distinction of two working periods, differing by their annual radon concentration (before/since 1956) does not modify this exposure-response relationship. This coefficient of risk per unit of exposure is lower than in most of the other uranium miners' studies but it lies in the range of the evaluation of the ICRP 50 committee and the 'BEIR IV' report of the U.S. National Academy of Science. It is observed in a cohort having experienced low cumulative exposure to radon (mean: 70 WLM) spread over a mean duration of 14.5 years. Even though occupational exposure in mines differs in several particulars from domestic exposure, this study presents characteristics of low annual exposure comparable to radon gas concentrations in houses of 500-1000 Bq.m-3, and will contribute to the evaluation of cancer risk for the public.

[Importance of the role of dose rate on tumor induction in rats after radon inhalation]. / Importance du rôle du débit de dose sur l'apparition des cancers chez le rat après inhalation de radon.

Lung cancer can be induced in rats, by radon daughter products, after exposure as low as 25 WLM (80 mJ.h.m-3) protracted over 4 to 6 months with a dose rate of 100 to 150 WL (2 to 3 mJ.m-3). The incidence of lung cancer is not increased and is equal to that of controls when the same cumulated dose is protracted over 18 months at 2 WL (0.042 mJ.m-3).

Epidemiological study of French uranium miners.

An epidemiological cohort study has been carried out to demonstrate any excess cancer mortality in a group of French uranium miners who worked underground for at least 2 years. The latency period of cancer associated with this type of professional exposure was long (10 to 20 years). The first study includes miners who began underground mining between 1946-1972. The individual monthly exposure to radon and its decay products has been recorded since 1956. The exposure of the first 10 years had to be estimated retrospectively for each miner regarding the working conditions. Problems associated with these two different exposure recordings are discussed. The results revealed an excess of lung cancer mortality for miners who had begun underground mining during the years 1946-1956.

Increased biopterin production in rats with tumors induced by radon inhalation and benzonaphthoflavone administration.

Serial determinations of urinary biopterin were performed in rats during the development of lung tumors induced by radon inhalation and 5,6-benzonaphtoflavone administration. A striking increase in biopterin levels was observed in animals which developed single or multiple epidermoid carcinoma of the lung and this increase occurred several weeks before tumors could be detected radiographically.

Lung carcinomas in Sprague-Dawley rats after exposure to low doses of radon daughters, fission neutrons, or gamma rays.

The effectiveness of radon-daughter inhalation and irradiation with fission neutrons and gamma rays in the induction of lung carcinomas in Sprague-Dawley rats at low doses is compared. Earlier reports which compared radon-daughter inhalations and neutron irradiations over a wider range of doses were based on dosimetry for the radon-daughter inhalations which has recently been found to be faulty. In the present analysis, low-dose experiments were designed to derive revised equivalence ratios between radon-daughter exposures, and fission neutron or gamma irradiations. The equivalence is approximately 15 working level months (WLM) of radon daughters to 10 mGy of neutrons (the earlier value was 30 WLM to 10 mGy). The relative biological effectiveness (RBE) of neutrons is 50 or more at a gamma-ray dose of 1 Gy. In these experiments with low doses and exposures, the lifetime incidences can be estimated from the raw incidences, while the derivation of the time dependence of the prevalence is essential for the estimation of RBE values and equivalence ratios.

Translocation of subcutaneously injected chrysotile fibres: potential cocarcinogenic effect on lung cancer induced in rats by inhalation of radon and its daughters.

Exposure to radon 222 and its daughters has been shown to induce lung cancer in rats. The cocarcinogenic effect of intrapleurally injected mineral fibres in rats which have previously inhaled radon has also been established. The aim of this work was to establish whether a similar process could be induced at a distance from the lungs by subcutaneous injection of chrysotile fibres. Three groups of animals were used: (1) 109 rats which inhaled radon only (dose: 1600 working-level months (WLM]; (2) 109 rats given a subcutaneous injection in the sacrococcygeal region of 20 mg of chrysotile fibres after inhalation of the same dose of radon; and (3) 105 rats injected with fibres only. No mesotheliomas occurred in any of the 3 groups. The incidence of lung cancer was 55% in group 2, 49% in group 1 and 1% in group 3. Statistical analysis using Pike's model showed that the carcinogenic insult was slightly higher in group 2 than in group 1. Electron microscopy analysis of fibre translocation from the injection site showed that less than 1% of injected fibres migrated to the regional lymph-nodes and only about 0.01% to the lungs. After injection, the mean length of the fibres recovered in lung parenchyma increased with time, suggesting that short fibres are cleared by pulmonary macrophages whereas long fibres are trapped in the alveolar walls. Although the high tumour incidence observed in group 1 might have masked the cocarcinogenic effect induced by the fibres, it is possible that this effect can occur only at short distances.(ABSTRACT TRUNCATED AT 250 WORDS)

[Colorectal anastomoses with a Steichen-type rectoplasty adapted by Dubois. Analysis of a series of 46 patients]. / Anastomoses colo-rectales avec rectoplastie de type Steichen adaptée par Dubois. Analyse d'une série de 46 opérés.

The authors report the results of a latero-lateral colorectal anastomotic technique which includes a wide rectoplasty. Analysis is based on 46 patients with a post-operative follow-up of between 2 and 8 years. 1 patient suffered from congenital mega-colon and 45 from adenocarcinoma of the upper half of the rectum. 4 of the anastomoses followed colostomy for obstruction and 4 others were followed by a protective colostomy. Two post-operative deaths occurred and there were 3 anastomotic fistulae, one of which was asymptomatic. Hepatic metastases occurred in 10 cases and were associated with loco-regional recurrence in 5 cases. The functional results were excellent. In survivors with no evidence of local recurrence there were no cases of stenosis of the anastomosis.

[Results of surgical treatment of cancer of the common bile duct as a function of age]. / Résultats du traitement chirurgical des cancers de la voie biliaire principale en fonction de l'âge.

The aim of this study was to determine whether an age greater than 70 years constitutes a risk factor in subjects who undergo surgery for cancer of the common bile duct. From a total population of 758 cases, 216 patients belonged to this age group. Tumour lesions did not appear to be more progressive in patients over 70 years, however there was a significantly higher incidence of visceral involvement in the latter group. The rate of palliative procedures was comparable in the under 70 and over 70 years groups. However, hepatectomy and hepatic transplantation were only carried out in patients under 70 years. Mortality increased with age both for palliative and curative surgery. The mortality rates were respectively 10% and 10.1% under 70 years and 41% and 49.1% over 70 years. These results should therefore lead to the choice of endoscopic drainage procedures in more elderly patients. However, in the absence of a contraindication to anaesthesia, surgery remains indicated when curative resection is envisaged, in cases of distal stenosis of the bile duct or for failure of other methods.

[Lymphangioma of the uterus. Apropos of a case]. / Lymphangiome du corps utérin. A propos d'un cas.

Lymphangioma of the uterine corpus is a rare tumor and the authors report one case discovered per-operatively. A review of the literature permits to bring out its essential characteristics as far as clinic, etiopathogenesis, evolution and therapy are concerned. This completely benign tumor is more an anatomo-pathological curiosity than a true gynecological problem.

[Antibiotic prophylaxis in surgery by vaginal route]. / Antibioprophylaxie dans la chirurgie par voie basse.

The authors study 56 cases of vaginal hysterectomy divided in two groups of 28, one of which received antibiotics prophylaxis at the time of the procedure. The incidences on post-operative fever, infection of the vaginal section and the number of urinary infections are significantly much lower in the group treated.

[A rare form of benign tumor of the liver possibly related to the use of oral contraceptives: focal pediculated nodular hyperplasia]. / Une forme rare de tumeur bénigne du foie en relation possible avec l'utilisation de contraceptifs oraux: "l'hyperplasie nodulaire focale pédiculée".

Following a recent case, the authors review the literature of hepatic nodular hyperplasia. The incidence of this condition increases regularly with the consumption of oestrogens. They attempt to define the methods of detection for patients at highest risk. Without exaggerating the incidence of this complication of oral contraceptives, the authors believe that it will become increasingly more common than the vascular complications which, although frequently discussed, are relatively rare.

PIP: This article describes a case of focal pedunculated nodular hyperplasia, a rare form of benign liver tumor, and reviews the literature on focal nodular hyperplasia (FNH) and hepatocellular adenoma. Focal pedunculated nodular hyperplasia is the rarest form of FNH and accounts for fewer than 20% of cases. Hepatocellular adenoma is usually a single encapsulated tumor ranging in size from 1-30 cm in diameter. FNH is usually also a single tumor which is always polylobed and multinodular. The size is variable and it is well defined although not encapsulated. Microscopically neither FNH nor hepatocellular adenoma has normal portal spaces or centrolobular veins. A peliose (intratumoral pseudomicrocysts) is often observed in oral contraceptive (OC) users in both cases. Atypical, dysplasic, or neoplasic cells are observed in about 10% of cases of hepatocellular adenoma but have never been reported in FNH. Considerable hypervascularization is found in hepatocellular adenoma but not in FNH, although in FNH large vascular pedicel may be observed at the periphery. Both tumors are most frequently seen in fertile aged women. Over 1/3 of cases of hepatocellular adenoma are discovered due to intraperitoneal bleeding. FNH is asymptomatic in 73.5% of cases and hemoperitoneum is very rare. The case reported was that of a 40-year-old woman with no significant medical history who had used a combined OC containing ethinyl estradiol and norgestrel for 6 years until 2 years previously, when she terminated use due to subsequently controlled hypertension. A 6-month history of menorrhagia was uncontrolled despite use of an OC containing levonorgestrel only. The liver tumor was discovered in the course of a total hysterectomy performed because of a large polymyomatous uterus associated with significant menorrhagia. The FNH was surgically removed 2 months later. The tumor was highly vascularized and connected to segment 4 by a voluminous pedicel containing numerous thick vascular elements. The postoperative course was smooth. The relationship between OC use and benign hepatic tumors is now well established. Their overall frequency has been estimated at 4.9/million women aged 15-45. The duration of exposure to OCs seems to be a determining factor. The risk is negligible at durations of OC use under 1 year but is multiplied by 7 for FNH and by 5 for hepatocellular adenoma after 5 years. EE, mestranol, and 19 norsteroids all seem to play etiologic roles. 58% of hepatocellular adenomas in OC users are discovered because of hemoperitoneum following rupture. Bleeding is usually massive and the mortality rate is about 6%. FNH is revealed by bleeding in 15% of cases in OC users and is asymptomatic in 49% of users. Tumor development depends on whether OC use is continued. It is not currently known whether the tumors tend in the long run to degenerate into hepatic carcinoma, and whether OC use plays a role. The occurrence of liver cancer in OC users does not seem to be greater than in the general population, but OC users are younger at diagnosis, their survival time is longer, and alpha fetoprotein levels are not elevated. Surveillance of OC users is difficult because FNH is so often asymptomatic. Periodic sonograms after 5 years of OC use may be indicated.

[Acupuncture in obstetrics]. / Acupuncture en obstétrique.

Acupuncture has been used in China as a treatment modality for one thousand years and is becoming increasingly important in the western world. Through a special effect on the reticular formation, acupuncture is becoming a first choice among the various methods available to relieve pain, especially in the pregnant woman. It can be useful, in fact, during the three periods of a pregnancy: before delivery: it can effect all the functional and psychiatric problems a pregnant woman may develop; during delivery: there is a definite analgesic and oxytocic effect; after delivery: it can be beneficial in all difficulties with breast feeding. Acupoints used in obstetrics are not very numerous. There are approximately thirty which are located along the body meridians or on the ear.

Incidence of various types of thoracic malignancy induced in rats by intrapleural injection of 2 mg of various mineral dusts after inhalation of 222Ra.

After inhalation of 222Ra at equilibrium with radon daughters, male Sprague-Dawley rats were inoculated intrapleurally with 2 mg of unleached or acid-leached asbestos fibres or glass fibres or quartz. The additive co-carcinogenic effects of this type of insult were demonstrated by the increased incidence of malignant thoracic tumours. In rats given mineral materials, bronchopulmonary carcinomas and mixed carcinomas were observed, as well as typical mesotheliomas and combined pulmonary pleural tumours, whereas in control rats inhaling radon alone, only bronchopulmonary carcinomas occurred. No significant differences in tumour incidence were observed between the groups of animals given the different types of dusts, but statistically significant differences were noted in survival times, according to the histological type of tumour. The co-carcinogenic effects of an insult of the pleura by mineral dusts following inhalation of radon are discussed in relation to a possible tumour-promoting effect by these agents.

Biological effects observed in mammals maintained in an area of vey high natural radioactivity.

Male rabbits (Oryctolagus cuniculus) were maintained for a 28-month period on the floor of the hut built at a site in southwestern France where the dose rate from natural radioactivity amounts to about 8 mrad/h. Male and female BALB/c mice (Mus musculus) were also placed in the hut during the summer period. The observations performed on those animals demonstrate that exposure to high natural radiation can increase the frequency of chromosome aberrations in somatic cells and indicate also the fertility in males and females is affected in an inverse manner. Model experiments with radon exposure of laboratory rabbits under controlled conditions have shown that the chromosome aberrations observed in somatic cels cella are not due to the radon exposure but essentially to gamma irradiation.