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Apparent synergy between chrysotile asbestos and N-nitrosoheptamethyleneimine in the induction of pulmonary tumours in rats
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related to duration of employment. None of these results is substantially altered when expected numbers are calculated from Cheshire urban areas rather than national rates, although the relative risks for lung cancer and non-malignant respiratory disease are substantially reduced if rates for Merseyside, the nearest large conurbation, are used. The results provide strong evidence that exposure to mustard gas can cause cancersoftheupperrespiratmy tractandsomeevidencethat itcancause lung cancer and non-malignant respiratory disease. Significant excess mortality wasalsoobserved forcancersoftheoesophagus(20observed. 10.72 expected) and stomach (70 observed, 49.57 expected) but these excesses showed no consistent relation with time since first exposure or duration of exposure, and it is not clear whether they were caused by mustard gas or were due to a combination of chance and confounding.
The epidemic of respiratory cancer in the town of Armadale: The use of long-term epidemiological surveillance to test a causal hypothesis. Williams FLR, Lloyd OL. Environmental Epidemiology and Cancer Cenrre, Deparrmenr of Communiiy Medicine, Ninewells Medical School, University ofDundee, Dundee. Public Health 1988;102:531-8.
In 1978, a geographical association was reported between air pollution from a steel foundry and high mortality from lung cancer in the adjacentresidential area of the town of Annadale, Scotland. Subsequent studies validated the mortality findings for lung cancer, demonstrated other epidemiological abnormalities, and examined the detailed patterns of environmental pollution. We summarise these findings and also report the outcome of the follow-up surveillance which demonstrated the end of the epidemic of lung cancer, both in the town as a whole and in the ‘at risk’ area. The sequence of epidemiological, environmental and industrial events was consistent with the hypothesis that air pollution from a steel foundry was causally linked with the short-latency epidemic of lung cancer in the town.
An estimate of adult mortality in the United States from passive smoking. Wells AJ. 102 Kildonan Glen. Wilmington, DE 19807. Environ Int
1988;14:249-65. The purpose of this paper is to estimate the number of adult deaths per year in the United States from passive smoking. The epidemiological literature on passive smokmg and adult mortality and cancer and heart morbidity is reviewed. Combined relative risks for lung cancer, cancers other than lung, and heart disease are calculated for each sex and disease category. These data along with estimates of nonsmoker death rates and populations exposed allow calculation of annual deaths in each category. Reduced relative risk and reduced exposure atolderages are taken into account as well as a correction for possible misclassification of smokers as nonsmokers and exposed nonsmokers as nonexposed. Altogether 46,000 deaths per year are calculated consisting of lung cancer (3000) other cancer (11,000) and heart disease (32,000). Reasons why such high estimates for other cancer and heart disease may be posstble am explored. It is concluded that exposure to environmental tobacco smoke can have adverse long term health effects that are more serious than previously thought.
Reanalysis of lung cancer mortality in a National Cancer Institute study on mortality among industrial workers exposed to formaldehyde. Sterling TD, Weinkam JJ. Faculty of Applied Sciences, School of Computing Science, Smon Fraser University, Burnaby. BC V5A IS6
J Occup Med 1988;30:895-901. The results of an hrstorical cohort study of mottahty among individualsoccupationallyexposedtofomialdehydewereannouncedin 1986by Blairetal (JNCI 1986; 76: 1071-1084). Thestudywasajointundertaling of the National Cancer Instttute and the Formaldehyde Institute, and concluded, ‘...thisIargemultiplantcohortstudy providedlittleevidence to suggest that formaldehyde exposures affected the mortality experience of these industrial workers.’ However, there were concerns by a numberofworkersthatthedesignandanalysisofthestudy hadpossibly masked an existing occupational hazard. Analyzing time-integrated
exposuretofonaldehydewithoutsimultaneouslyconsideringlengthof exposure and comparing mortality of formaldehyde workers to mortality of the general population could have masked an increase in cancer risksbecauseofthehealthyworkereffect.Acopyofthedataofthestudy was obtained from the principal investigator and reanalyzed. We find a signilicantly increased risk for all cancers and for lung cancer as a function of cumulative exposure when workers wuh higher levels of exposure are compared with those with little or no exposure while simultaneouslyconsideringlenghtofexposure. Whentheriskratio(RR) for lung cancer at _ 0. I ppm cumulative exposure (CX) is taken as I .O, the lung cancer RR for CX of 0.1 to 0.5 ppm is 1.41 (1.20 to 1.66), the RR for CX of 0.5 to 2.0 ppm is 1.73 (1.42 to 2.1 I). and the RR for CX _ 2.0 is 1.70 (1.32 to 2.18). Hourly workers have a significantly higher RR than salaried workers (RR = 1.58). Similar increased RRs are observed for all cancers and all causes. The RRs for different length of exposure are not significantly elevated because of the mathematical relationshipbetweencumulativeexposure,lengthofexposure,andlevel of exposure and because of the possibility that workers exposed to very high levels of exposure may tend to leave employment early.
Apparent synergy between chrysotile asbestos and N-nitrosobep tamethyleneimine in the induction of pulmonary tumours in rats. Harrison PTC, Heath JC. Strangeways Research L.aborntory. Cambridge CBI 4RN. Carcinogenesis 1988;9:2165-71.
Environmental carcinogenesis in man is widely accepted to be a multifactorial process, and in the causation of lung cancers it is suspected that low levels of systemic carcinogens may act synergtstitally with inhaled particulates so that some exposed individuals are at increased risk. In thepresentstudy the carcinogenic effectsof low levels of industrially/environmentally significant particulate materials (chrysotilc asbestos and metallic cadmium) and a putative systemic carcinogen,N-niuosoheplamethyleneimine(NHMI),wereinvestigated in the laboratory rat, using this as a model of potential human exposure. The overall lung tumour incidence rate in the groups of animals receivmg chrysotile and NHMI together (S/50) or chrysotile, cadmium and NHMI together (6/44) was substantially higher than in the groups receiving chrysotile alone (I/86) or chrysotile and cadmium (19/4) or NHMIalone(2/48). Theresultsdemonstratedapparentsynergybetween chrysotile and NHMI in the induction of lung turnours. Incidence of pulmonary hyperplastic lesions paralleled the trend in tumotn inctdence.Cadmium hadlittleornoinfluenceontheincidenceofeitherlung tumours or hyperplastic lesions. Thts study helps to evaluate further the roleofasbestosmthecausationoflungcancer. Itissuggested thatpeople who are or have been exposed to chrysotile asbestos may show a significantly elevated risk of lung cancer if concomuantly or suhsequently exposed to tumour initiating agents. Etfects of palytoxin or ouabain on growth and squamous differentiation of human bronchial epithelial cells in vitro. Bonnard C, Lechner JF, Gerwin BI, Fujiki H, Harris CC. Nestle Research Center, Nestec Ltd. CH-1020 Lmsanne. Carcmogenesis
1988;9:2245-9. The effects of the non-12.0.terradecanoylphorbol-13-acetate type tumor promoter palytoxin on human bronchial epithelial cells was studied in an in vitro serum-free culture system. Unlike the results of prevtousstudies withanothertumorpromoter, 12-O-tetmdecanoylphorbo-13-acetate, palytoxin did not induce squamous differentiation of normal bronchial epithelial cells and was equally cytotoxtc for normal human bronchial epithelial cells, a human lung tumor cell line, and human bronchial epithelial cells immortalized by infection wuh adenovirus 12SV40hybrid virus (BEAS-2B cells). Palytoxin did not Induce a change m free cytosolic Ca2*concentration of BEAS-2B cells. The effect of palytoxin on the c-myc mRNA steady state level in BEAS-2B cells was studied: 1pM palytoxin Increased the steady-state level at 12 and 18 h. Furthermore, the induction was accompanied by an mcrcase in [‘Hlthymidineuptake. Becausepalytoxin bmds to(Na’+K’)ATPase, the effects of ouabain were compared to the effects of palytoxin. A ouabain-resistant cell line wasa sensitive to the growth inhibuory effect of palytoxin as the parent ouabam-sensitive cell line, suggesting different binding sites to the (Na’ + K+)-ATPase for palytoxin and ouabain. Ouabain also increased the steady-state level of c-myc gene expression,
related to duration of employment. None of these results is substantially altered when expected numbers are calculated from Cheshire urban areas rather than national rates, although the relative risks for lung cancer and non-malignant respiratory disease are substantially reduced if rates for Merseyside, the nearest large conurbation, are used. The results provide strong evidence that exposure to mustard gas can cause cancersoftheupperrespiratmy tractandsomeevidencethat itcancause lung cancer and non-malignant respiratory disease. Significant excess mortality wasalsoobserved forcancersoftheoesophagus(20observed. 10.72 expected) and stomach (70 observed, 49.57 expected) but these excesses showed no consistent relation with time since first exposure or duration of exposure, and it is not clear whether they were caused by mustard gas or were due to a combination of chance and confounding.
The epidemic of respiratory cancer in the town of Armadale: The use of long-term epidemiological surveillance to test a causal hypothesis. Williams FLR, Lloyd OL. Environmental Epidemiology and Cancer Cenrre, Deparrmenr of Communiiy Medicine, Ninewells Medical School, University ofDundee, Dundee. Public Health 1988;102:531-8.
In 1978, a geographical association was reported between air pollution from a steel foundry and high mortality from lung cancer in the adjacentresidential area of the town of Annadale, Scotland. Subsequent studies validated the mortality findings for lung cancer, demonstrated other epidemiological abnormalities, and examined the detailed patterns of environmental pollution. We summarise these findings and also report the outcome of the follow-up surveillance which demonstrated the end of the epidemic of lung cancer, both in the town as a whole and in the ‘at risk’ area. The sequence of epidemiological, environmental and industrial events was consistent with the hypothesis that air pollution from a steel foundry was causally linked with the short-latency epidemic of lung cancer in the town.
An estimate of adult mortality in the United States from passive smoking. Wells AJ. 102 Kildonan Glen. Wilmington, DE 19807. Environ Int
1988;14:249-65. The purpose of this paper is to estimate the number of adult deaths per year in the United States from passive smoking. The epidemiological literature on passive smokmg and adult mortality and cancer and heart morbidity is reviewed. Combined relative risks for lung cancer, cancers other than lung, and heart disease are calculated for each sex and disease category. These data along with estimates of nonsmoker death rates and populations exposed allow calculation of annual deaths in each category. Reduced relative risk and reduced exposure atolderages are taken into account as well as a correction for possible misclassification of smokers as nonsmokers and exposed nonsmokers as nonexposed. Altogether 46,000 deaths per year are calculated consisting of lung cancer (3000) other cancer (11,000) and heart disease (32,000). Reasons why such high estimates for other cancer and heart disease may be posstble am explored. It is concluded that exposure to environmental tobacco smoke can have adverse long term health effects that are more serious than previously thought.
Reanalysis of lung cancer mortality in a National Cancer Institute study on mortality among industrial workers exposed to formaldehyde. Sterling TD, Weinkam JJ. Faculty of Applied Sciences, School of Computing Science, Smon Fraser University, Burnaby. BC V5A IS6
J Occup Med 1988;30:895-901. The results of an hrstorical cohort study of mottahty among individualsoccupationallyexposedtofomialdehydewereannouncedin 1986by Blairetal (JNCI 1986; 76: 1071-1084). Thestudywasajointundertaling of the National Cancer Instttute and the Formaldehyde Institute, and concluded, ‘...thisIargemultiplantcohortstudy providedlittleevidence to suggest that formaldehyde exposures affected the mortality experience of these industrial workers.’ However, there were concerns by a numberofworkersthatthedesignandanalysisofthestudy hadpossibly masked an existing occupational hazard. Analyzing time-integrated
exposuretofonaldehydewithoutsimultaneouslyconsideringlengthof exposure and comparing mortality of formaldehyde workers to mortality of the general population could have masked an increase in cancer risksbecauseofthehealthyworkereffect.Acopyofthedataofthestudy was obtained from the principal investigator and reanalyzed. We find a signilicantly increased risk for all cancers and for lung cancer as a function of cumulative exposure when workers wuh higher levels of exposure are compared with those with little or no exposure while simultaneouslyconsideringlenghtofexposure. Whentheriskratio(RR) for lung cancer at _ 0. I ppm cumulative exposure (CX) is taken as I .O, the lung cancer RR for CX of 0.1 to 0.5 ppm is 1.41 (1.20 to 1.66), the RR for CX of 0.5 to 2.0 ppm is 1.73 (1.42 to 2.1 I). and the RR for CX _ 2.0 is 1.70 (1.32 to 2.18). Hourly workers have a significantly higher RR than salaried workers (RR = 1.58). Similar increased RRs are observed for all cancers and all causes. The RRs for different length of exposure are not significantly elevated because of the mathematical relationshipbetweencumulativeexposure,lengthofexposure,andlevel of exposure and because of the possibility that workers exposed to very high levels of exposure may tend to leave employment early.
Apparent synergy between chrysotile asbestos and N-nitrosobep tamethyleneimine in the induction of pulmonary tumours in rats. Harrison PTC, Heath JC. Strangeways Research L.aborntory. Cambridge CBI 4RN. Carcinogenesis 1988;9:2165-71.
Environmental carcinogenesis in man is widely accepted to be a multifactorial process, and in the causation of lung cancers it is suspected that low levels of systemic carcinogens may act synergtstitally with inhaled particulates so that some exposed individuals are at increased risk. In thepresentstudy the carcinogenic effectsof low levels of industrially/environmentally significant particulate materials (chrysotilc asbestos and metallic cadmium) and a putative systemic carcinogen,N-niuosoheplamethyleneimine(NHMI),wereinvestigated in the laboratory rat, using this as a model of potential human exposure. The overall lung tumour incidence rate in the groups of animals receivmg chrysotile and NHMI together (S/50) or chrysotile, cadmium and NHMI together (6/44) was substantially higher than in the groups receiving chrysotile alone (I/86) or chrysotile and cadmium (19/4) or NHMIalone(2/48). Theresultsdemonstratedapparentsynergybetween chrysotile and NHMI in the induction of lung turnours. Incidence of pulmonary hyperplastic lesions paralleled the trend in tumotn inctdence.Cadmium hadlittleornoinfluenceontheincidenceofeitherlung tumours or hyperplastic lesions. Thts study helps to evaluate further the roleofasbestosmthecausationoflungcancer. Itissuggested thatpeople who are or have been exposed to chrysotile asbestos may show a significantly elevated risk of lung cancer if concomuantly or suhsequently exposed to tumour initiating agents. Etfects of palytoxin or ouabain on growth and squamous differentiation of human bronchial epithelial cells in vitro. Bonnard C, Lechner JF, Gerwin BI, Fujiki H, Harris CC. Nestle Research Center, Nestec Ltd. CH-1020 Lmsanne. Carcmogenesis
1988;9:2245-9. The effects of the non-12.0.terradecanoylphorbol-13-acetate type tumor promoter palytoxin on human bronchial epithelial cells was studied in an in vitro serum-free culture system. Unlike the results of prevtousstudies withanothertumorpromoter, 12-O-tetmdecanoylphorbo-13-acetate, palytoxin did not induce squamous differentiation of normal bronchial epithelial cells and was equally cytotoxtc for normal human bronchial epithelial cells, a human lung tumor cell line, and human bronchial epithelial cells immortalized by infection wuh adenovirus 12SV40hybrid virus (BEAS-2B cells). Palytoxin did not Induce a change m free cytosolic Ca2*concentration of BEAS-2B cells. The effect of palytoxin on the c-myc mRNA steady state level in BEAS-2B cells was studied: 1pM palytoxin Increased the steady-state level at 12 and 18 h. Furthermore, the induction was accompanied by an mcrcase in [‘Hlthymidineuptake. Becausepalytoxin bmds to(Na’+K’)ATPase, the effects of ouabain were compared to the effects of palytoxin. A ouabain-resistant cell line wasa sensitive to the growth inhibuory effect of palytoxin as the parent ouabam-sensitive cell line, suggesting different binding sites to the (Na’ + K+)-ATPase for palytoxin and ouabain. Ouabain also increased the steady-state level of c-myc gene expression,