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Biomedical subjects

H Vainio

Publications and source records attributed to H Vainio.

At least 127 records · Page 7Linked to original sources
PubMed1994

Asbestos exposure and the risk of lung cancer in a general urban population.

OBJECTIVES: The aim of the study was to investigate the asbestos-associated risk of lung cancer according to histological type of cancer, lobe of origin, pulmonary concentration, and type of amphibole fibers and also to estimate the etiologic fraction of asbestos for lung cancer. METHODS: The pulmonary concentration of asbestos fibers in 113 surgically treated male lung cancer patients and 297 autopsy cases among men serving as referents was determined by scanning electron microscopy. The age- and smoking-adjusted odds ratios of lung cancer were calculated according to pulmonary fiber concentration for all lung cancer types, squamous-cell carcinoma, and adenocarcinoma and for the lower-lobe and the upper- and middle-lobe cancers. RESULTS: The risk of lung cancer was increased according to the pulmonary concentration of asbestos fibers (f) of 1.0 to 4.99 x 10(6) f.g-1 [odds ratio (OR) 1.7] and > or = 5.0 x 10(6) f.g-1 (OR 5.3). The odds ratios associated with fiber concentrations of > or = 1.0 x 10(6) f.g-1 were higher for adenocarcinoma (OR 4.0) than for squamous-cell carcinoma (OR 1.6). The asbestos-associated risk was higher for lower lobe tumors than for upper lobe tumors. The risk estimates for anthophyllite and crocidolite-amosite fibers were similar, except for the risk of squamous-cell carcinoma. An etiologic fraction of 19% was calculated for asbestos among male surgical lung cancer patients in the greater Helsinki area. CONCLUSIONS: Past exposure to asbestos is a significant factor in the etiology of lung cancer in southern Finland. The asbestos-associated risk seems to be higher for pulmonary adenocarcinoma and lower-lobe tumors than for squamous-cell carcinoma and upper-lobe tumors.

Adult↗
PubMed1994

Mechanisms of the combined effect of asbestos and smoking in the etiology of lung cancer.

The joint effects of exposure to two known lung carcinogens, tobacco smoking and asbestos, are reviewed. The variable pattern of interaction--ranging from supramultiplicative to less than additive--may reflect the fact that both asbestos and smoking are complex carcinogens which can affect more than one stage of lung carcinogenesis. The joint effect of two such agents will depend on the relative magnitude of the effects at each stage. The epidemiologic evidence from studies of insulation workers with high exposures suggests an interaction that approximates the multiplicative model, indicating that each of the two factors has an independent action on the multistage process of carcinogenesis. Very limited information is available on the interaction between these two agents in causing specific histological types of lung cancer. Both tobacco smoke and asbestos fibers can be genotoxic and cytotoxic and cause proliferative lesions in the lungs. Tobacco smoke is known to contain carcinogens that bind to critical genes in DNA (deoxyribonucleic acid) and cause mutations. Asbestos fibers may cause chronic inflammation of the lungs, which releases various cytokines and growth factors, and therefore may provide a possible selective growth advantage for mutated cells.

Asbestos↗
PubMed1994

Occupational exposures to carcinogens in developing countries.

There have been very few studies of exposure to occupational carcinogens in developing countries, and even fewer studies of the health consequences of such exposures. However, all industrial chemicals, occupations and industrial processes classified by the International Agency for Research on Cancer (IARC) as Group 1 or Group 2A (carcinogenic or possibly carcinogenic to humans) have been described in developing countries, and there is growing concern that the health impact of many chemicals used in the developing world has been underestimated. In all regions a very large workforce is employed in the construction industry, in which substantial exposure to asbestos may occur, and there has been a rapid increase in production in countries such as Brazil and India. There is, for instance, a similar pattern for tyre production with a large increase in production in developing countries in the 1980s. Thus, the number of workers in industries entailing a carcinogenic risk is increasing in developing countries, partly as a result of the transfer of hazardous industry from industrialized countries. There is much that could be achieved in the prevention of occupational cancer in developing countries, and there have been a number of successful initiatives. However, the greatest progress in the prevention of occupational cancer in developing countries is most likely to come from political and economic changes.

Carcinogens↗
PubMed1994

Increased incidence of lung and skin cancer in Finnish silicotic patients.

Cancer incidence during 1953 to 1991 in 811 Finnish silicotic patients diagnosed between 1936 and 1977 was evaluated. In comparison with the general population, excesses were observed for all cancers (standardized incidence ratio, 1.7 [95% confidence interval, 1.4 to 1.9]), all lung cancers (2.9 [2.4 to 3.5]), squamous cell lung cancers (3.3 [2.3 to 4.5]), and skin cancers: melanoma (3.0 [0.8 to 7.6]) and nonmelanoma (2.9 [1.2 to 6.1]). Confounding by tobacco smoking did not explain the lung cancer increment. The consistency of the association between silicosis and lung cancer across a large number of studies suggests that silicosis represents a direct or indirect lung cancer hazard. The skin cancer excess, a relatively novel finding, may be explained either by carcinogens in foundries, or silica-induced lowering of immunocompetence, which would lead to a more pronounced effect of solar ultraviolet radiation.

Adult↗
PubMed1993

Immunohistochemical localization of glutathione S-transferases in human lung.

Glutathione S-transferases (GST) detoxify a number of carcinogenic electrophiles including diol-epoxide metabolites of polycyclic aromatic hydrocarbons. The distribution of GSTs A1/A2, M1, M2, M3, and P1 has been studied in lung tissue from 32 subjects by immunohistochemistry using rabbit polyclonal antibodies. GSTA1/A2 and GSTP1 were found to be the most abundant GSTs in human lung, being present in the bronchial and bronchiolar epithelium of all individuals studied. The staining intensity for GSTA1/A2 varied more than that for GSTP1 between individuals. GSTM1, a polymorphic mu-class enzyme, was ambiguously detected in lung tissue and, if expressed, is present at very low levels. GSTM2, a striated muscle-specific isozyme, occurred minimally in the epithelium of the terminal airways, and GSTM3, an enzyme of broad extrahepatic occurrence, was observable in the ciliated airway epithelium and smooth muscle of the lung. The staining for GSTM3 varied from minimal to very intense between individuals; in the bronchial epithelium, it was more abundant in current smokers than in exsmokers. The immunostaining for GSTs in general was most intense in the bronchial epithelium decreasing in the distal airways, in contrast to the previously described peripheral localization of the polycyclic aromatic hydrocarbons activating the P450IA1 enzyme. The localization of GSTs in the bronchial wall suggests that GST polymorphisms may contribute to susceptibility, especially to bronchial tumors of tobacco smokers.

Adult↗
PubMed1993

Cytochrome P450-related differences between rats and mice in the metabolism of benzene, toluene and trichloroethylene in liver microsomes.

In evaluating the risks to humans of exposure to chemicals, the results of studies in rodents are sometimes used as a basis for extrapolation. It is therefore important to elucidate differences in metabolism among species. Differences in cytochrome P450-catalysed oxidation of benzene, toluene and trichloroethylene (TRI) between male Wistar rats and male B6C3F1 mice were investigated by immunoblot and immunoinhibition assays using monoclonal antibodies (MAbs) to cytochrome P450 (CYP1A1/2, CYP2B1/2, CYP2E1 and CYP2C11/6). Immunoblot analysis showed that anti-CYP2B1/2 did not detect any protein in either untreated rat or mouse liver microsomes, whereas with anti-CYP2E1 and/or anti-CYP1A1/2 a clear-cut band was seen more in liver microsomes from mice than from rats. Mouse liver microsomes had a greater monooxidation activity for benzene and TRI than rat liver microsomes; mice also had a higher rate of aromatic hydroxylation of toluene at low substrate concentration, but a low rate of side-chain oxidation when a high concentration of toluene was used. The metabolism of benzene was saturated in mice at around 0.23 mM, but the metabolism of the other two solvents was not saturated in either rats or mice at the low concentrations used. Anti-CYP2E1 inhibited the metabolism of benzene, toluene and TRI in microsomes from mice to a greater extent than in rats, while anti-CYP2C11/6 inhibited their metabolism in rats to a greater extent than in mice; anti-CYP1A1/2 inhibited the metabolism of TRI only in microsomes from mice. These results indicate that (i) male B6C3F1 mice have more CYP2E1 and 1A1/2 than male Wistar rats, whereas rats have more CYP2C11/6 than mice; (ii) rats and mice express CYP2B1/2 but they are not immunochemically detectable; (iii) CYP2E1 and 2C11/6 in both species are responsible for the metabolism of benzene, toluene and TRI, whereas CYP1A1/2 in mice catalyses the oxidation of TRI. The differences in the metabolism of benzene, toluene and TRI in rats and in mice may therefore depend, at least in part, on differences in the distribution of P450 isozymes between the two species.

Animals↗
PubMed1993

K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos.

We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed--in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation--a clear association of K-ras mutations with heavy life-time smoking (> or = 50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2-19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6-8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.

Adenocarcinoma↗
PubMed1993

Asbestos exposure among Finnish lung cancer patients: occupational history and fiber concentration in lung tissue.

In a series of 65 surgically treated lung cancer patients, past exposure to asbestos was evaluated by personal interviews, and by scanning electron microscopy analyses of the mineral fibers in lung tissue. Lung tissue samples of 17 autopsied male office workers were analyzed as referents. According to occupational history, 37% of the lung cancer patients had definite or probable, 31% possible, and 32% unlikely exposure to asbestos. The fiber concentration in the lung tissue ranged from < 0.1 to 65 million fibers per gram dry tissue in the lung cancer group, and from < 0.1 to 0.8 million fibers per gram dry tissue in the reference group. In 26% of the lung cancer patients, but in none of the referents, the fiber concentration exceeded 1 million fibers per gram dry tissue. Most of the exposed patients had been employed in various construction jobs, and valuable information about the exposure levels could be obtained by the mineral fiber analyses. In general, there was a good accord between the exposure categorization and the fiber burden measured in the lung.

Adenocarcinoma↗
PubMed1993

Maternal smoking induced cotinine levels and genotoxicity in second trimester amniotic fluid.

Cotinine concentrations in amniotic fluid samples from 22 smoking and 37 non-smoking pregnant women and induction of sister-chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells by samples from 15 smokers and 15 non-smokers were studied as indicators of exposure to potential genotoxic activity during pregnancy. Analysis of cotinine revealed one individual in the non-smoking group with a high cotinine level apparently due to non-reported smoking. The mean cotinine concentration of smokers was 85 ng/ml whereas non-smokers had a concentration of 0.3 ng/ml. According to interview data 16 persons announced some passive exposure to tobacco smoke at home or at work; however this group did not differ from unexposed non-smokers in their amniotic fluid cotinine concentration. SCE inducing activity was tested with and without metabolic activation. The mean SCE frequency in CHO cells induced in the presence of exogenous metabolic activation by concentrated amniotic fluid of heavy smokers (> or = 10 cigarettes/day) was significantly higher (9.7 +/- 0.6 SCE/cell) than among non-smokers (8.9 +/- 0.6 SCE/cell) with metabolic activation. The results show that amniotic fluid cotinine measurements and induction of SCEs in CHO cells can be used to indicate fetal exposure by maternal smoking and support earlier studies suggesting a potential genotoxic hazard to the fetus of heavy smokers.

Adult↗