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Biomedical subjects

H Vainio

Publications and source records attributed to H Vainio.

At least 109 records · Page 6Linked to original sources
PubMed1995

Coffee consumption not associated with risk of pancreas cancer in Finland.

BACKGROUND: Coffee consumption has been brought to focus as a possible risk factor for pancreas cancer. After having reviewed the available evidence, an International Agency for Research on Cancer working group concluded in 1991 that the evidence in humans that coffee drinking is carcinogenic in the pancreas is "inadequate," since the available data were considered suggestive of a weak relationship with high levels of coffee consumption, but the possibility that this was due to bias or confounding was judged tenable. METHODS: The association between coffee consumption and pancreas cancer risk was examined in a case-referent study in Finland. Data on coffee consumption 20 years prior to the diagnosis of cancer were obtained from the next of kin of 662 cases of pancreas cancer and 1,770 referent (stomach, colon, and rectum) cancers. The results were expressed as crude and age-, gender-, and tobacco smoking-adjusted odds ratios and 95% confidence intervals for three daily coffee dose categories 20 years prior to cancer diagnosis. RESULTS: The data failed to demonstrate any association between coffee consumption and risk for pancreas cancer. The crude odds ratios varied between 0.7 (95% confidence interval 0.3-1.5) and 1.3 (0.7-2.6), the adjusted ones between 0.5 (0.2-1.2) and 1.1 (0.6-2.1) in the different daily dose categories of coffee and between contrasts with the three referent cancers. The highest odds ratios were associated with the contrast between pancreas and colon cancer, the lowest between pancreas and rectum cancer. Adjustment for gender, age, and tobacco smoking slightly decreased the values of the odds ratios. The power of the study was low, however, to detect possible weak increases associated with coffee consumption. CONCLUSIONS: The results are unlikely to be negatively biased, and are compatible with the majority of epidemiologic results advanced, suggesting no positive association between coffee consumption and the risk of pancreas cancer.

Case-Control Studies↗
PubMed1995

Different contributions of cytochrome P450 2E1 and P450 2B1/2 to chloroform hepatotoxicity in rat.

The contribution of cytochrome P450 isozymes CYP2E1 and CYP2B1/2 to chloroform-induced hepatotoxicity taken at 18 hr after the treatment was investigated in rats treated with n-hexane as an inducer of CYP2E1, 2-hexanone as an inducer of CYP2E1 and CYP2B1/2, and phenobarbital (PB) as an inducer of CYP2B1/2. Hepatic damage was evaluated by gross measurement of plasma alanine aminotransferase activity and histopathological examination. All treatments potentiated chloroform-induced hepatic damage. In n-hexane-pretreated rats, the damage was maximal with the middle dose of chloroform (0.2 ml/kg), whereas the damage increased with dose in rats treated with 2-hexanone or PB. The degree of hepatic damage induced with the three pretreatments was in the following order: n-hexane > 2-hexanone = PB with the middle dose of chloroform and PB >> 2-hexanone > n-hexane with the high dose (0.5 ml/kg); little difference among the pretreatments was seen with the low dose (0.1 ml/kg). These findings suggest that CYP2E1 is a low Km isoform and CYP2B1/2 a high Km isoform for chloroform activation. CYP2E1-dependent hepatic damage was characterized by ballooned hepatocytes, which were restricted to the centrilobular area; with CYP2B1/2, more necrotic than ballooned hepatocytes were seen and the necrotic hepatocytes were found not only in the centrilobular but also in the midzonal and periportal areas. Chloroform treatment did not affect the activity of N-nitrosodimethylamine N-demethylase in pretreated rats; the high dose increased the activity in control rats. In contrast, the high dose of chloroform decreased the activity of 7-pentoxyresorufin O-depentylase in all induced rats but not in controls. Immunoinhibition and immunoblot analyses showed that the high dose of chloroform induced CYP2E1 in control rats but decreased CYP2B1/2 in all pretreated rats. These results suggest that although both CYP2E1 and CYP2B1/2 contribute to chloroform-induced hepatic damage, they do so quite differently.

Alanine Transaminase↗
PubMed1995

PCDD/PCDF levels in the blood of workers at a pulp and paper mill.

Blood samples from 34 workers at a pulp and paper mill and from 14 control persons were analysed for 2,3,7,8-substituted PCDDs and PCDFs. There were no statistically significant differences in total lipid-adjusted PCDD/PCDF concentrations, expressed as toxic equivalents, in blood plasma between the potentially exposed bleaching plant or paper mill workers and the controls. The mean level was 61 pg/g I-TEQ in bleaching plant workers, 60 pg/g I-TEQ in paper mill workers and 49 I-TEQ pg/g in controls. Regarding the concentrations of individual isomers, however, there was an indication that the blood plasma concentrations might be affected by the living and working environment.

Adult↗
PubMed1995

Expression and polymorphism of glutathione S-transferase in human lungs: risk factors in smoking-related lung cancer.

The relationships between smoking and the expression of glutathione S-transferase (GST*) isozymes GSTM1-1, GSTM3-3, GSTP1-1 and GSTA1-1/2-2 (GSTA1/2), or between smoking and activities of epoxide hydrolase (EH) and aryl hydrocarbon hydroxylase (AHH) were investigated in lung samples from 27 patients with lung cancer and 11 control patients by immunoblot analysis and enzyme assays. Determination of genotypes in blood leucocyte DNA showed that possession of the mu-class GSTM1 gene was closely related to the expression of GSTM1-1 and GSTM3-3 enzymes in lung cytosol: patients with the GSTM1 null genotype had no detectable GSTM1 protein and less GSTM3 protein than patients with the GSTM1 gene (P < 0.001). Absence of the GSTM1 gene did not affect the content of phi-class GSTP1-1 or alpha-class GSTA1/2. GST activity towards 1-chloro-2,4-dinitrobenzene was lower (P < 0.01) in patients lacking the GSTM1 gene than in those expressing GSTM1; in general, patients with a low GSTM3-3, GSTP1-1 or GSTA1/2 content also had significantly less overall GST activity. The pulmonary content of GSTP1-1 was greater in cancer than in non-cancer patients (P < 0.05). Smoking did not influence the levels of GST isozymes or the EH activity. In contrast, the AHH activity was significantly (P < 0.01) increased by smoking. Neither AHH nor EH showed a correlation with GSTM1 polymorphism. Our data support the idea that in smokers who lack the GSTM1 gene, activation of carcinogens in tobacco smoke (e.g. benzo[alpha]pyrene) is increased, while the efficacy of detoxification is limited both qualitatively (absence of GSTM1-1 enzyme and low expression of GSTM3-3 enzyme) and quantitatively (low overall GST activity). This imbalance in the metabolism of carcinogens may explain the increased susceptibility to lung cancer reported in smokers with the GSTM1 null genotype.

Animals↗
PubMed1995

Molecular approaches in toxicology: change in perspective.

Molecular approaches have attained a central position in modern experimental and human toxicology by providing the means to study basic underlying mechanisms. Molecular methods can be used to identify causal associations that would otherwise be obscure and to make better quantitative estimates of those associations at relevant levels of exposure. They may also make it possible to identify susceptible groups or individuals who are at risk of suffering the toxic effects of certain types of environmental and occupational agents. The use of transgenic animals in toxicology will improve our understanding of the role of toxic chemicals, such as carcinogens and mutagens, and their dosimetry and target organs. The use of molecular approaches in toxicology should thus result in better estimates of risks to human health.

Animals↗
PubMed1995

p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures.

This paper reviews mutational activation of ras oncogenes and inactivation of the p53 tumor suppressor gene in human lung cancer. We discuss the frequency, type, and location of mutations in these genes in relation to known etiological factors for lung cancer. The most studied examples of these are exposure to tobacco smoke, and to radon and asbestos fibers at work. We summarize data from our laboratory on K-ras and p53 mutations in fresh tissue samples from patients with resected primary lung carcinoma whose smoking and occupational histories were known. Most of the tumors examined were histologically non-small cell carcinoma (NSCLC), mainly of the squamous cell carcinoma and adenocarcinoma types. We compare the prevalence and nature of mutations in the two histological types of NSCLC.

Genes, p53↗
PubMed1995

[Identification of human carcinogenic risks in IARC monographs].

For more than twenty years, the IARC has been evaluating the carcinogenic risk to humans of chemicals, groups of chemicals, complex mixtures, occupational exposures, behavioral and life-style exposures, biological agents, such as bacteria and viruses, and physical agents, such as radiation, on the basis of published studies of carcinogenicity in humans and laboratory animals. This paper includes the list established by IARC of substances carcinogenic to humans.

Animals↗
PubMed1994

CYP2C11 and CYP2B1 are major cytochrome P450 forms involved in styrene oxidation in liver and lung microsomes from untreated rats, respectively.

The contribution of cytochrome P450s (P450s) to the formation of styrene glycol from styrene in rat liver microsomes was investigated using monoclonal antibodies to P450s. Anti-CYP2E1 inhibited the formation to a similar extent in ethanol-treated microsomes and in control microsomes in terms of percentage inhibition, whereas to a greater extent in the former than the latter in terms of net inhibition, and only at low substrate concentration. Anti-CYP2C11/6 also inhibited the formation in control and in ethanol-treated microsomes at both low and high concentrations of styrene, and the net degree of inhibition was greater than that obtained with anti-CYP2E1, even in ethanol-treated microsomes where CYP2E1 was induced. Anti-CYP2B1/2 and anti-CYP1A1/2 inhibited the formation only in phenobarbital (PB)- and 3-methylcholanthrene (MC)-induced microsomes, respectively. These results suggest that (1) at least four P450s, CYP2C11/6, CYP2E1, CYP2B1/2 and CYP1A1/2, contribute to the metabolism of styrene, (2) CYP2C11/6, which probably corresponds to CYP2C11, is the major form of P450 responsible for the metabolism in untreated rat liver microsomes, and also in those treated with ethanol. Anti-CYP2E1 inhibited styrene oxidation more prominently in microsomes from styrene-treated rats than in those from control rats at a low substrate concentration. Although styrene treatment did not influence the total metabolism of styrene in liver microsomes at a high substrate concentration, inhibition of the metabolism by anti-CYP2C11/6 decreased with increasing styrene dose, whereas that by anti-CYP2B1/2 increased, suggesting that styrene treatment increases CYP2B1/2 but decreases CYP2C11/6 in rat liver, and the major form of P450 which mediates styrene oxidation is CYP2B1/2 after the treatment. Only anti-CYP2B1/2, which probably corresponds to CYP2B1, inhibited styrene oxidation in lung microsomes from untreated and even styrene-treated rats. Thus, the major form of P450 responsible for the metabolism of styrene is different in each tissue.

Animals↗
PubMed1994

Detection of increased amounts of the extracellular domain of the c-erbB-2 oncoprotein in serum during pulmonary carcinogenesis in humans.

Over-expression of the c-erbB-2 oncogene-encoded p185 protein product has been implicated in the pathogenesis of a wide variety of human malignancies, including lung cancer. Over-expression of p185 can be detected immunologically by quantification of the extracellular domain of p185 (c-erbB-2 oncopeptide) in extracellular fluid in vitro and in serum in vivo. An enzyme-linked immunosorbent assay (ELISA) for the c-erbB-2 oncopeptide was used to examine banked serum samples of 11 pneumoconiosis patients who subsequently developed lung cancer and serum samples from 11 hospital controls matched for age, sex, ethnic group and smoking as well as 55 unmatched general population controls. The mean serum level for the c-erbB-2 oncopeptide in human neu units/ml in the lung cancer cases (1,756 +/- 549 HNU/ml) was statistically significantly elevated (p < 0.001) in comparison to the mean level in the matched controls (976 +/- 488 HNU/ml) or the general population controls (888 +/- 655 HNU/ml). Defining a positive elevation of the serum c-erbB-2 oncopeptide as any value more than 2 standard deviations above the mean of the matched controls, 64% (7 of 11) of the lung cancer cases were positive compared to 0% (0 of 11) matched controls and 5% (3 of 55) of the unmatched controls. In addition, 4 of the 7 c-erbB-2 oncopeptide-positive cancer cases had positive serum samples prior to the time of disease diagnosis (average = 35 months). These results suggest that serum c-erbB-2 oncopeptide may be elevated at an early stage of pulmonary carcinogenesis and that further prospective study of the utility of this biomarker is warranted.

Aged↗
PubMed1994

Genotoxicity of kraft pulp spent liquors from different types of chlorination procedures.

The genotoxicity of spent liquors from kraft softwood and hardwood pulp bleaching processes was studied using the Ames Salmonella test and the SOS chromotest. The induction of micronuclei, in vivo, was assayed in bone marrow erythrocytes of B6 mice treated with softwood first chlorination stage spent liquor. The softwood bleaching process used a combination of Cl2 and ClO2 at the first chlorination stage. During the study the amount of free chlorine at the first chlorination stage in the softwood bleachery was gradually decreased, although the amount of active chlorine remained the same. Enzymatic bleaching was also used in a softwood process together with chlorine (Cl2 + ClO2). The hardwood bleaching plant used only ClO2 at the first chlorination stage. A decrease in genotoxicity, corresponding to the decrease in Cl2, was observed in the Ames Salmonella assays of the softwood bleaching plant effluents. A similar decrease was observed in the SOS chromotest. The highest decrease in mutagenic activity was observed when enzymatic bleaching was used together with chlorine.

Animals↗
PubMed1994

Modulation of urinary mutagenicity by genetically determined carcinogen metabolism in smokers.

We examined the genotypes of two polymorphic genes involved in the detoxification of several mutagenic and carcinogenic compounds in relation to tobacco smoking-associated urinary mutagenicity. The genes studied were the glutathione S-transferase-encoding GSTM1 gene and acetyltransferase-encoding NAT2 gene. Smokers with no GSTM1 gene (n = 7) had urine that was several times more mutagenic than that of smokers with the gene (n = 10). The mean level of urinary mutagenicity in presence of metabolic activation was 2527 +/- 958 revertants/100 ml urine for GSTM1-smokers compared to 766 +/- 560 revertants/100 ml for GSTM1+ smokers (P < 0.001) using the bacterial strain YG1024. The corresponding values using the TA98 strain were 336 +/- 124 and 123 +/- 75 (P < 0.001). In contrast, we failed to show any difference in the level of urinary mutagenicity between slow-acetylator and fast-acetylator NAT2 genotypes among smokers (n = 17) or non-smokers (n = 35). Our results offer one explanation for the recent findings that GSTM1 polymorphism is a risk modifier in smoking-related cancers, especially bladder cancer.

Arylamine N-Acetyltransferase↗
PubMed1994

Combined effect of CYP1A1 inducibility and GSTM1 polymorphism on histological type of lung cancer.

The combinations of the CYP1A1 inducibility and GSTM1 polymorphism have been investigated in relation to the histological type and peripheral or bronchial location of lung cancer in 54 surgically treated, current smoker lung cancer patients. The induced CYP1A1 was detected in 46 patients (85%) and the homozygous GSTM1 null genotype in 32 patients (59%). The role of CYP1A1 inducibility was found to be more important than that of GSTM1 polymorphism, because the non-inducible CYP1A1 was associated solely with bronchial tumours (P = 0.001), mainly squamous cell carcinomas. In patients with inducible CYP1A1, the expressing GSTM1 gene appeared to have a protective effect against contracting bronchial lung cancer, since 88% (14/16) of the lung tumours in this patient group were peripheral, whereas almost equal numbers of peripheral and bronchial tumours were observed in those patients lacking the gene (P = 0.037).

Aryl Hydrocarbon Hydroxylases↗
PubMed1994

Detection of serum p53 protein in lung cancer patients.

Serum levels of p53 protein were examined in 23 cases of lung cancer (many with potential asbestos exposure), 23 unexposed matched hospital control subjects, 58 unmatched general population control subjects, and 4 people with nonmalignant lung disease using an enzyme-linked immunosorbent assay and Western immunoblotting. Average levels of serum p53 in the lung cancer patients (0.55 ng/mL) were higher than in the cases of nonmalignant lung disease (0.42 ng/mL) or in the matched (0.32 ng/mL) or unmatched (0.31 ng/mL) control subjects, but the differences were not statistically significant. However, three of the cases of lung cancer (13%) were found to have serum p53 levels much greater than those of the control subjects (> 2 SD above the mean) and to have confirmatory positive Western blots for p53. The tumors from these subjects demonstrated increased levels of p53 in the tissue by immunohistochemistry and/or the presence of mutations in the p53 gene. These results suggest that p53 protein can be detected in serum in a portion of lung cancer cases with p53 alterations in the tumor tissue.

Aged↗