Ambulatory blood pressure characteristics in normotensive and treated hypertensive older people.

The objective of this study was to determine the normal values and characteristics of 24-h ambulatory blood pressure (ABP) and to describe the ABP level of treated hypertensive subjects in an older Finnish population. ABP was measured in 502 randomly selected subjects aged 64 years or over living in a Finnish municipality (mean age 70 years, range 64-87 years). A total of 211 subjects did not have blood pressure (BP) affecting medication. ABP measurements were taken every 30 min for 24 h, and the day- and night-time periods were diary-based. The results were that in untreated subjects, the average office BP was 134/82 +/- 16/9 (s.d.) mm Hg for men and 140/81 +/- 18/8 mm Hg for women. The 24-h average BP was 120/75 +/- 14/8 mm Hg (95th percentile upper limit 145/93 mm Hg) for men and 125/75 +/- 15/7 (95th = 154/89 mm Hg) for women. The daytime averages were 127/78 +/- 12/7 mm Hg (95th = 154/99 mm Hg) and 131/78 +/- 15/7 mm Hg (95th = 158/91 mm Hg) for men and women, respectively. The ABP daytime value of 130/83 mm Hg corresponded best to the office BP value of 140/90 mm Hg. All BP values were significantly higher in the treated hypertensive group compared to the normotensive group. Night-time BP was markedly lower than daytime BP, and no difference in circadian variability was found between the normotensive and hypertensive subjects. Both office and ambulatory BPs were significantly higher in women than in men. This study provides sex-specific normal values for ABP in a 64 to 87-year-old age group. The normal values of ABP were markedly lower than the office BP values. Hypertensives, even when treated, tended to have elevated values.

Ambulatory blood pressure and left ventricular mass in older age.

BACKGROUND: The purpose of this study was to analyse the association of ambulatory blood pressure (ABP) to left ventricular mass (LVM) in a population aged over 64 years and to describe the level of ABP in subjects with and without left ventricular hypertrophy (LVH) in older age. METHODS: ABP measurement and echocardiography for calculation of LVM were assessed in 490 inhabitants (mean age 70.7 years, range 64-87 years) of a small town in southwestern Finland who were able to visit an outpatient clinic. Explanatory factors associated with LVM were assessed with linear regression analysis. LVH was defined as calculated LVM-index values exceeding 150 g/m2 in men and 120 g/m2 in women adopted from the Framingham Study. RESULTS: Systolic ABP was significantly associated with LVM. No correlation between diastolic ABP and LVM was found. Other factors independently related to LVM were gender, body mass index and age. The prevalence of echocardiographic LVH was 22%. Subjects with LVH had markedly higher systolic ABP levels than those without LVH (mean (SD) 24-h ABP: 132(16)/75(8) mmHg vs. 123(13)/75(8) mmHg). CONCLUSION: Systolic ABP is associated with LVM in older people. In addition, systolic ABP is superior to diastolic ABP in relation to LVM in the aged.

Long-term reproducibility of ambulatory blood pressure in unselected elderly subjects.

The aim of this study was to evaluate the long-term reproducibility and validity of 24-h ambulatory blood pressure measurements (ABPM) in an unselected elderly population. In a rural Finnish community 503 randomly chosen invited persons over 65 years of age participated and went through 24-h ABPM. As part of the validation of the methodology, the reproducibility study was conducted in 26 persons (age 65-76 years). Two identical sets of measurement were performed at 4-12 (median 8) month intervals. The agreement between measurements was assessed by correlation coefficients and standard deviation (SD) of the differences. There were no significant differences in 24-h, daytime and night-time average diastolic blood pressure (DBP) and daytime average systolic blood pressure (SBP) between the two measurements. During the second measurement, 24-h SBP and night-time average SBP were slightly higher than those obtained by the first monitoring. Average 24-h SBP and DBP were 18 and 7 mmHg lower, respectively, than office blood pressure averages. The correlation coefficients were significantly higher for 24-h ambulatory blood pressure than for office blood pressure. The SD of the mean difference between visits was significantly lower for 24-h ambulatory blood pressure than for office blood pressure measurements. These findings show that the long-term reproducibility of ambulatory blood pressure is good in an elderly unselected population and better than the office blood pressure reproducibility.

Asthma and gastro-oesophageal reflux: can the response to anti-reflux therapy be predicted?

The aim of the study was to investigate which features predict favourable response to omeprazole therapy in asthmatics with gastro-oesophageal reflux (GER). The study population consisted of 52 outpatient asthmatics with GER who had completed an intervention where they were randomized to receive omeprazole 40 mg once a day or placebo for 8 weeks. After a 2-week washout period the patients were crossed over. Asthma symptoms were found to be relieved > or = 20% in 18 (35%) patients who were thus regarded as responders. A logistic regression analysis was performed in order to identify which features separate the responders from the non-responders. More responders were found among the patients whose body mass index (BMI) was higher (P = 0.02) or whose distal esophageal reflux was more severe [total time (%) pH < 4 (P = 0.01) or time (%) pH < 4 in upright position (P = 0.04)]. Adding other predictors to the total time (%) pH < 4, which was the most significant predictor for response in multi-variate analysis, did not further increase the prediction for favourable outcome. It is concluded that severe distal oesophageal reflux and obesity predict amelioration in asthma symptoms after 8-week omeprazole treatment in asthmatics with GER. Adding more than one predictor does not seem to further increase prediction for favourable asthma response.

Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole.

Gastro-oesophageal reflux (GOR) is an important cause of chronic cough. There has been a lack of placebo-controlled trials treating GOR related chronic cough with antireflux therapy. The aim of this study was to determine the efficacy of omeprazole on GOR related chronic cough. After excluding other common causes of cough, oesophageal pH monitoring was performed on 48 patients with chronic cough. Twenty-nine patients found to have GOR were randomized in a double-blind fashion to receive omeprazole 40 mg o.d. or placebo for 8 weeks. After a 2-week washout period, patients were crossed over to the other treatment. Symptoms were recorded daily in a diary. Twenty-one patients completed both treatment periods. Cough (p=0.02) and gastric symptoms (p=0.003) improved significantly during the omeprazole treatment in twelve patients who received placebo during the first and omeprazole during the second 8-week period. In nine patients who received omeprazole during the first 8-week period, amelioration in cough reached statistical significance only after cessation of omeprazole. Gastric symptoms also remained minor during placebo in these nine patients. Omeprazole 40 mg o.d. seems to improve chronic cough in patients with gastrooesophageal reflux and the effect of omeprazole in ameliorating both cough and reflux symptoms continues after treatment ceases.

Relationship between lipid peroxidation and plasma fibrinogen in middle-aged men.

The relationship between lipid peroxidation (plasma malondialdehyde [MDA] concentration) and plasma fibrinogen level was analyzed in 144 men, aged 53-62 years. MDA was measured colorimetrically and fibrinogen with the thrombin method. Mean plasma MDA concentration was 12.6 (SD 1.2) micromol/L, plasma fibrinogen level 2.91 (0.47) g/L, and body mass index 27.1 (3.5) kg/m(2). Prevalence of smoking was 17%. MDA correlated moderately with fibrinogen. Both MDA and fibrinogen correlated positively with waist hip ratio (WHR) and blood leukocyte count, but inversely with VO(2)max. Both MDA and fibrinogen levels were higher in smokers than in non-smokers (p<0. 01). In multiple stepwise regression analysis, plasma MDA, VO(2)max, smoking, and leukocyte count explained 38.1% of the variance in plasma fibrinogen level, with the individual contributions reaching 20.6%, 9.7%, 5.5%, and 2.3%, respectively. WHR, serum triglycerides, and age did not enter the model. These data suggest that increased lipid peroxidation is associated with elevated plasma fibrinogen level in middle-aged men.

Lipid peroxidation status, somatic mutations and micronuclei in peripheral lymphocytes: a case observation on a possible interrelationship.

A controlled dietary study was conducted in healthy female volunteers and reported elsewhere [1]. In a subset of samples four different biomarkers were analyzed: plasma malondialdehyde (MDA) levels and urinary 8-isoprostaglandin-F(2alpha) were measured as markers for lipid peroxidation. The frequency of hprt (hypoxanthine guanine phosphoribosyl transferase) mutants and micronuclei in peripheral blood lymphocytes were analyzed as indicators of genotoxic effects. One of the ten individuals showed extremely high background levels in all of the four endpoints measured. This case observation raises the possibility that life style factors and dietary habits affect the level of DNA reactive lipid peroxidation products, which in turn increase mutagenic and cytogenetic effects. A possible association between these biomarkers, particularly in relation to dietary fat intake and antioxidant status, should now be studied in a larger trial.

Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole.

STUDY OBJECTIVES: To investigate the prevalence of gastroesophageal reflux (GER) among patients with asthma and to determine the effect of omeprazole on the outcome of asthma in patients with GER. DESIGN: A double-blind, placebo-controlled crossover study. SETTING: Asthmatic patients who attended the pulmonary outpatient clinic of Turku University Central Hospital, Finland. PATIENTS: One hundred seven asthmatic patients. INTERVENTIONS: The patients who were found to have GER in ambulatory esophageal pH monitoring were randomized to receive either omeprazole, 40 mg qd, or placebo for 8 weeks. After a 2-week washout period, the patients were crossed over to the other treatment. Spirometry was performed at baseline and immediately after both treatment periods. Peak expiratory values, use of sympathomimetics, and pulmonary and gastric symptoms were recorded daily in a diary. RESULTS: Pathologic GER was found in 53% of the asthmatic patients. One third of these patients had no typical reflux symptoms. Daytime pulmonary symptoms did not improve significantly (p = 0.14), but a reduction in nighttime asthma symptoms (p = 0.04) was found during omeprazole treatment. In the patients with intrinsic asthma, there was a decline in [corrected] FEV(1) values (p = 0.049). Based on symptom scores, 35% of the patients were regarded as responders to 8-week omeprazole treatment. The reflux (time [percent] of pH < 4) was found to be more severe (p = 0. 002) in the responders. CONCLUSIONS: There is a high prevalence of GER in the asthmatic population. This reflux is often clinically "silent." After an 8-week omeprazole treatment, there was a reduction in nocturnal asthma symptoms, whereas daytime asthma outcome did not improve. There seems to be a subgroup of asthma patients who benefit from excessive antireflux therapy.

Green tea extract decreases plasma malondialdehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy females.

BACKGROUND: Green tea contains polyphenolic catechins which can act as antioxidants and thus decrease the risk for cardiovascular diseases. AIM OF THE STUDY: To investigate whether green tea extract differs from placebo in its effects on markers of antioxidant status, lipid peroxidation, nitric oxide production, thromboxane production, and blood coagulation during a controlled high linoleic acid diet in healthy subjects. METHODS: Twenty healthy non-smoking females (23-50 years) participated in a 4-week controlled intervention study. The experimental diet was rich in linoleic acid (9 en%) and contained fat, protein, and carbohydrates: 27, 14, and 59 en%, respectively. In addition, the subjects ingested encapsulated green tea extract (3 g/d) or placebo mixture in a double-blind manner. Fasting blood samples and five 24-hour urines were collected before and at the end of the 4-week experimental period. Same samples were received from 10 control subjects. RESULTS: Green tea extract significantly decreased plasma malondialdehyde (MDA) concentration in comparison with the placebo treatment. The treatments did not differ in serum lipids, indicators of antioxidant status, urinary 8-isoprostaglandin F2 alpha, 2,3-dinorthromboxane B2, nitric oxide metabolites or coagulation indicators. CONCLUSIONS: We conclude that an amount of green tea extract which corresponds to 10 cups of tea per day for 4 weeks does not have specific effects on several indicators related to risk of cardiovascular diseases in comparison with placebo treatment. The relatively small but significant decrease in lipid peroxidation indicated by decreased plasma MDA was not associated with changes in markers of oxidative stress (urinary 8-isoprostaglandin F2 alpha and blood oxidized glutathione) or hemostasis.

Significance of graft occlusion and coronary atherosclerosis 5 years after coronary artery bypass grafting. A quantitative angiographic study with serial exercise testing.

OBJECTIVE: To evaluate the relative importance of graft occlusions and progression of atherosclerosis in coronary arteries as causes of the occurrence of angina pectoris and impairment of physical performance 5 years after coronary artery bypass surgery. DESIGN: A 5-year follow-up study. SETTING: University hospital in south-western Finland. SUBJECTS: Altogether, 174 consecutive electively operated bypass patients. MAIN OUTCOME MEASURES: Serial clinical evaluation and bicycle exercise tests (pre-operatively, at 6 months, and at 1 and 5 years). Quantitative coronary angiography pre-operatively and 5 years after the surgery. RESULTS: Subjects with patent grafts had fewer angina pectoris symptoms at the 5-year follow-up (24 vs. 52%, P = 0.001) and were treated less frequently with long-acting nitrates (3 vs. 15%, P = 0.037) than subjects with graft occlusions. Fewer of them were in classes II-III of the functional classification of the Canadian Cardiovascular Society (39 vs. 74%, P = 0.001). The exercise test was interrupted less often because of chest pain (23 vs. 41%, P = 0.03) and improvement in exercise test variables during the follow-up period was significantly greater in subjects with patent grafts (P<0.002). Amongst patients without graft occlusions, those with new > or =50% diameter stenoses in coronary arteries were more often in functional classes II-III (59 vs. 32%, P = 0.03) than those without new stenoses, but the groups were similar with respect to angina pectoris and exercise tests variables. In patients with graft occlusions, those with and without new > or =50% diameter stenoses were similar with respect to functional class, angina pectoris and exercise test variables. CONCLUSIONS: Angina pectoris and impairment of physical capacity 5 years after coronary artery bypass grafting are mainly due to occlusion of bypass grafts and not to progression of atherosclerosis in coronary arteries.

Little effect of ordinary antihypertensive therapy on nocturnal high blood pressure in patients with sleep disordered breathing.

The antihypertensive effects of four different antihypertensive medications (beta-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM). Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM. Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD+/-14) mm Hg with atenolol, 7 (SD+/-10) mm Hg with isradipine SRO, 3 mm Hg (SD+/-14) with HCTZ, and 6 (SD+/-15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50. Negative correlation was observed between the apnea time and the mean systolic 24-h (r = -0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = -0.590, P = NS). Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.

Interaction between dose and susceptibility to environmental cancer: a short review.

Increased risk of environmentally induced cancer is associated with various types of exposures and host factors, including differences in carcinogen metabolism. Since many carcinogenic compounds require metabolic activation to enable them to react with cellular macromolecules, individual features of carcinogen metabolism may play an essential role in the development of environmental cancer. In this context, cigarette smoking has often been the main type of carcinogenic exposure examined in human studies. Increasing attention has recently been paid to the dose level at which individual susceptibility may be observed. Present studies on increased risk of smoking-related lung cancer associated with phenotypic or genotypic variation of the genes encoding for CYP1A1 or CYP2D6 enzymes are summarized. Similarly, higher risks of lung or bladder cancer seen at various levels of smoking in association with polymorphism of the glutathione S-transferase gene GSTM1 or NAT1 and NAT2 genes involved in N-acetylation are reviewed. Finally, the influence of CYP2E1, GSTM1, or the combined at-risk genotype on the risk of hepatocellular carcinoma in smokers is briefly discussed.

Ambulatory blood pressure reproducibility and application of the method in a healthy Finnish cohort.

The aim of the present study has been to study the reproducibility, validity and normal values of ambulatory blood pressure measurement in a healthy Finnish cohort. The reproducibility of ambulatory blood pressure monitoring was examined in healthy volunteers and normal values were determined in a Finnish cohort of males and women of different ages. In the reproducibility study the recording was repeated at 2-week intervals. In the validity study simultaneous measurements were done manually with a mercury sphygmomanometer and compared with the measurement by the ambulatory blood pressure recording unit, both connected with the cuff by a T-tube; this study included 100 consecutive measurements in a patient group. A relatively small cohort was taken from the normal value study group. In addition to ambulatory blood pressure their left ventricle mass was also determined by echocardiography. The correlation between manual blood pressure measurement and simultaneous measurement by the ambulatory blood pressure unit was 0.98. In the reproducibility study the correlations between the two 24-h measurements 2 weeks apart were also good. Depending on the parameter (daytime, nighttime or 24-h blood pressure mean, systolic or diastolic values) the correlation coefficient varied between 0.81 and 0.91. Thus both systolic and diastolic blood pressures, whether expressed as 24-h averages and daytime or nighttime averages, correlated well between these two recording sessions. The data obtained in the present Finnish cohort were well within the published reference value limits, showing only fairly modest age-dependence appearing at quite an old age. There was no significant correlation between the left ventricle mass and ambulatory blood pressure values in a population having normal blood pressure. The results suggest good intra-individual correlation and reproducibility in ambulatory blood pressure monitoring, suggesting this method to be useful in the monitoring of individual blood pressure levels. The validity of the method is good and the published reference values can be applied with reasonable reliability in different populations. In an adult population with normal blood pressure, no correlation between left ventricle mass and blood pressure values can be found, suggesting this correlation may first appear in cohorts including persons with elevated blood pressure values.

The role of individual susceptibility in cancer burden related to environmental exposure.

Individual susceptibility to cancer may result from host factors including differences n metabolism, DNA repair, altered expression of protooncogenes and tumor suppressor genes, and nutritional status. Since most carcinogens require metabolic activation before binding to DNA, variations in an individual's metabolic phenotype that have detected in enzymes involved in activation and detoxification should play an essential role in the development of environmental cancer. This phenotypic metabolic variation has now been related to genetic polymorphisms, and many genes encoding carcinogen-metabolizing enzymes have been identified and cloned. Consequently, allelic variants or genetic defects that give rise to the observed variation and new polymorphisms have been recognized. Development of simple polymerase chain reaction (PCR)-based assays has enabled identification of an individual's genotype for a variety of metabolic polymorphisms. Thus, recent knowledge of the genetic basis for individual metabolic variation has opened new possibilities of studies focusing on increased individual susceptibility to environmentally induced cancer, which are reviewed with special reference to smoking-induced lung cancer. Cancer susceptibility due to chemical exposure is likely to be determined by an individual's phenotype for a number of enzymes (both activating and detoxifying) relevant to that of a single carcinogen or mixtures of carcinogens. Given the number and variability in expression of carcinogen-metabolizing enzymes and the complexity of chemical exposures, assessment of a single polymorphic enzyme (genotype) may not be sufficient. Mutations in the p53 gene are among the most common genetic changes in human cancer. The frequency and type p53 mutations can act as a fingerprint of carcinogen exposure and may therefore provide information about external etiological agents, intensity of exposure, and host factors affecting the tumorigenesis process. In human lung cancer, p53 mutations (both the mutation pattern and frequency) have been linked with tobacco smoking; the type of mutation most frequently observed is G:C to T:A transversion, a mutation preferentially induced by benzo[a]pyrene diol epoxide. An association between the presence of this transversion and the genotype deficient in glutathione S-transferase M1-mediated detoxification has been observed in lung cancer. Taken together, these findings suggest that determination of metabolic at risk genotypes in combination with levels of DNA adducts in target (surrogate) tissues and the p53 mutation pattern should allow the identification of susceptible individuals and subgroups in carcinogen-exposed populations.

A molecular and epidemiological study on bladder cancer: p53 mutations, tobacco smoking, and occupational exposure to asbestos.

In this study, we found an unexpected association (crude odds ratio = 2.8; 95% confidence interval = 0.9-8.4) between definite work-related exposure to asbestos and carcinoma of the urinary bladder in a small group of patients (n = 28) initially recruited as referents for an epidemiological feasibility study on the occupational causes of lung cancer. We extended the study by using molecular methods to examine mutations in the p53 tumor suppressor gene in the same cases of bladder cancers. The same number of archival samples of transitional cell carcinoma, mainly of grade 3, were added to the analysis. We failed to show any association between occupational exposure to asbestos and p53 mutations among bladder cancer patients. We observed an increasing occurrence of p53 mutations in nonsmokers (5 of 17, 29%), former smokers (8 of 21, 38%), and current smokers (9 of 16, 56%) in that order; however, this was not statistically significant. The most prevalent type of mutation was G:C to A:T transition. Tumor grade was not associated with the frequency of mutations, but the higher stage (T3-T4) tumors appeared to have mutations more frequently than did the less invasive tumors (T1-T2).

Validity of ambulatory 24-h oesophageal pH measurement in the diagnosis of reflux disease.

The validity of 24-h oesophageal pH recording was studied in 100 consecutive patients who had gastro-oesophageal reflux (GER) symptoms and had indications for a 24-h pH recording. The aim was to explore the relationship of patient symptoms, endoscopic findings and histopathological analysis of oesophageal mucosa with the findings in pH recording. Among these patients with typical GER symptoms, the multiplicity of symptoms or their nature did not differentiate them, but in all groups abnormal amounts of reflux were present, as compared with usual reference pH recording values. Yet, among these symptomatic patients, the macroscopic severity of oesophagitis and histologically defined oesophagitis were related to increased abnormality of 24-h pH recording. The results suggest that 24-h pH recording of the oesophagus gives a good indication of the severity of gastro-oesophageal reflux disease and, as such, superior to patient symptoms.

Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility--a review.

Up to 90% of all cancers are possibly caused by environmental factors, such as tobacco smoke, diet and occupational exposures. The majority of chemical carcinogens require metabolic activation before they interact with cellular macromolecules and can cause cancer initiation. The xenobiotic-metabolising machinery contains two main types of enzymes: the phase-I cytochromes P-450 (CYP) mediating oxidative metabolism, and phase-II conjugating enzymes. Several phase-I and phase-II genes have recently been cloned and identified in humans. Many of them show polymorphism and have been suggested to contribute to individual cancer susceptibility as genetic modifiers of cancer risk. Altered phenotypes and genotypes in the CYP subfamilies CYP1A1, CYP2D6 and CYP2E1 have been associated with tobacco smoke-induced lung cancer and other cancers. Defective glutathione S-transferase (GST) and N-acetyltransferase (NAT) enzymes have been associated with an increased risk of developing lung and bladder cancer. There are also several studies in each category in which no associations have been found. The risk of developing lung cancer is dramatically (up to 40-fold) elevated in subpopulations having simultaneously high-risk genotypes in CYP1A1 and GSTM1. There are several difficulties in this area of research. First, many of the observed restriction-fragment length polymorphisms (RFLPs) are due to mutations in introns or other silent areas of DNA, raising the possibility that any associations found between RFLPs and cancer occur only by chance. Second, biologically plausible mechanisms linking genotypes and cancer are lacking in most of the observed cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma and lipoprotein lipid peroxidation in humans on sunflower and rapeseed oil diets.

The effects of natural mixed diets on lipid peroxidation were investigated in humans. In the first study, 59 subjects were fed a rapeseed oil-based diet rich in monounsaturated fatty acids (MUFA) and a sunflower oil-based diet rich in polyunsaturated fatty acids (PUFA) in a cross-over manner for three and a half weeks. The lipid peroxidation products in plasma were determined by measuring conjugated dienes and malondialdehyde (MDA). In a second study, plasma thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and the susceptibility of very low density lipoprotein+low-density lipoprotein (LDL) to in vitro oxidation were measured from subjects fed similar MUFA and PUFA diets for six weeks diets. No significant differences in plasma MDA or conjugated diene concentrations were found after the rapeseed oil diet or the sunflower oil diet in Study 1. In the second study, a small but significant decrease (P < 0.05) in both lipid hydroperoxides and TBARS was observed in the LDL fraction after the sunflower oil diet. The in vitro oxidation gave opposite results, showing increased oxidation after the sunflower oil diet. Despite a high intake of alpha-tocopherol during the oil periods, no increase in plasma alpha-tocopherol was noticed in either study. The results suggest that moderate changes in the fatty acid composition in the Western-type diet may be adequate to affect lipoprotein susceptibility to oxidation in vitro, but there is considerable disparity with some indices of in vivo lipid peroxidation.

Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans.

A case-control study on lung cancer patients demonstrated the pronounced effect of tobacco smoke on pulmonary carcinogen metabolism and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer. Lung cancer patients who were recent smokers showed in their lungs (i) significantly induced CYP1A1-related enzyme activity vs smoking non-lung cancer patients; (ii) increased benzo(a)pyrene (BP) tetrol formation from BP 7,8-diol by lung microsomes; and (iii) high levels of cytochrome P4501a1 by immunohistochemical staining. Levels of bulky aromatic DNA adducts (by 32P-postlabelling) and of BP-diol-epoxide (BPDE) adducts (by HPC/fluorometry) were quantified in lung parenchyma. Aryl hydrocarbon hydroxylase activity and the level of BPDE-DNA adducts (r = 0.91; p < 0.001) and to a lesser degree bulky DNA adducts were correlated. Thus pulmonary CYP1A1 expression (inducibility) controls in part polycyclic aromatic hydrocarbon-DNA adduct formation in tobacco smokers and, therefore, appears to be associated with lung cancer risk. High risk subjects for lung cancer among smokers may be identifiable through genotyping for polymorphic drug metabolizing enzymes in combination with molecular dosimetry of carcinogen-DNA adducts and mutation analysis in target (surrogate) cells. Such studies in a Finnish cohort of lung cancer patients and controls are in progress. Interim results of the effect of metabolic polymorphism on the level of PAH-DNA adducts and on the excretion of mutagens in urine are summarized.