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We investigated the roles of EPHX1 Tyr 113 His and His 139 Arg polymorphisms in lung cancer susceptibility in a Finnish study population comprising of 230 lung cancer cases and a large control group ( n =2105). The controls were distributed into five age strata, which enabled us to examine the potential age-related changes in the putative EPHX1 at-risk genotypes in the cancer free population. Although the exon 3 slow activity associated allele ( His 113 ) containing genotypes posed a decreased lung cancer risk compared with the homozygous wild-type Tyr 113 / Tyr 113 genotype (OR, 0.68; 95% CI, 0.49–0.94), no association was seen for the EPHX1 phenotypes interpreted from the combined exons 3 and 4 genotype data. Neither was any difference seen in the prevalence of the EPHX1 Tyr 113 His genotypes or interpreted EPHX1 phenotypes in the different age groups.

Some 3-10% of Caucasians are deficient in CYP2D6 metabolism (poor metabolizers), due to inheritance of two defective alleles, whereas amplification of the CYP2D6 gene results in ultrarapid metabolism in 1-2% of Caucasian populations. To examine the possible association between CYP2D6 polymorphism and individual smoking behaviour, we analysed the prevalence of CYP2D6 genotypes among 292 long-term heavy smokers, 382 individuals with more variable smoking histories, and 302 never-smokers. The prevalence of ultrarapid metabolizers in heavy smokers (7.9%) was twofold compared to individuals with variable smoking habits (3.7%; odds ratio 2.3, 95% confidence interval 1.2-4.4), and fourfold compared with never-smokers (2.0%) (odds ratio 4.2, 95% confidence interval 1.8-9.8). The frequency of poor metabolizer genotype was approximately 2%, in each smoker group. However, when men and women were studied separately, the prevalence of poor metabolizer genotype was higher in male never-smokers (3.6%) than in variable smokers (2.7%) and heavy smokers (2.2%). Moreover, a trend test, adjusted by age, gender and cancer status, revealed a significant trend for the increased tobacco usage with increased metabolic capacity. Our results are in agreement with the assumption that increased CYP2D6 activity may contribute to the probability of being addicted to smoking.

Serum concentrations of apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] were studied with respect to age and sex in a Finnish population sample of 575 subjects (286 men and 289 women), ages 27-67 years. Apo A-I and apo B were measured with an immunoturbidimetric method calibrated against WHO International Reference Materials. Lp(a) was measured by RIA. Apo A-I and apo B concentrations were almost normally distributed (apo A-I: mean 1.38 g/L vs median 1.34 g/L for men, and 1.58 g/L vs 1.55 g/L for women; apo B: mean 1.21 g/L vs median 1.20 g/L for men and 1.09 g/L vs 1.05 g/L for women). The distribution of Lp(a) was remarkably skewed (mean 190 mg/L vs median 86 mg/L for men, and 169 mg/L vs 85 mg/L for women). The 95% intervals for apo A-I were 1.09-1.84 g/L for men and 1.06-2.28 g/L for women; for apo B, they were 0.63-1.88 g/L and 0.56-1.82 g/L, respectively. Apo A-I concentrations appeared to be unrelated to age, whereas apo B and Lp(a) concentrations were age-dependent. Cutoff values based on the 90th percentile for apo B and the 10th percentile for apo A-I are proposed for identifying subjects at increased risk of coronary heart disease.

Objective: To determine the accuracy of the estimation of serum low-density lipoprotein (LDL) cholesterol concentration by the Friedewald formula. Methods: Modifications of the calculation formula are presented on the basis of ultracentrifugal separation of serum high-density lipoprotein and LDL cholesterol in the specimens collected (n = 1215) in a nationwide health survey. Results: The formulas obtained from different subject groups differed relatively little from each other. The accuracy of the original Friedewald formula was poor; in about 36% of the subjects the error was more than 5% compared with ultracentrifugally obtained results. By applying the currently recommended coronary heart disease (CHD) risk categorizations, high proportions (5%–28%) of the subjects were classified into wrong CHD risk categories when LDL cholesterol was calculated with any of the formulas. At high serum triglyceride levels, misclassifications were especially common. Conclusions: We conclude that even the most accurate LDL cholesterol calculation methods should be used with caution while classifying subjects into categories of CHD risk. In hypertriglyceridemic subjects, the calculation formulas probably should not be used at all.

The reference intervals for the activities of L-alanine aminotransferase (EC 2.6.1.2, ALAT), L-aspartate aminotransferase (EC 2.6.1.1, ASAT) and gamma-glutamyltransferase (EC 2.3.2.2, GT) in serum were determined according to the recommendations of the European Committee for Clinical Laboratory Standards (ECCLS). Serum specimens from 954 subjects were analysed for ALAT and ASAT and from 794 subjects for GT. The subjects, aged 27-67 years, were participants in general health surveys. The reference population was formed by excluding subjects with any disease, or on any medication, affecting the liver, and also those consuming excessive amounts of alcohol. The 95% inner reference intervals for ALAT and ASAT were 9-50 (n = 189) and 15-36 U l-1 (n = 192) in men and 8-38 (n = 270) and 13-33 U l-1 (n = 270) in women. For GT the reference interval was 11-58 in men (n = 165) and 8-42 U l-1 in women (n = 220). Serum GT levels correlated clearly with alcohol consumption. Serum ALAT and ASAT were only slightly associated with alcohol consumption at levels less than 280 g per week in men and 190 g per week in women. There were modest positive associations between the three enzyme levels and body mass index. None of the enzymes correlated significantly with age.

Screening for gastrointestinal cancer is based mainly on a barium contrast x ray method and on identification of occult blood in stools. The methods are relatively expensive, not always acceptable to the participants, and there is only limited evidence of their effectiveness in reducing the mortality from gastrointestinal cancer. Objective - To investigate the validity of several tumour markers as a screening test for stomach cancer and for colorectal cancer. A registry of 36 265 serum samples drawn during 1968–72 was linked to the cancer registry. Follow up was during 1968–80 when 94 stomach cancers and 95 colorectal cancers were identified. One to two matched case-control design was applied, and the concentrations of CEA, CA 19–9, CA 50, and TATI were assessed. The mean values of the markers between the cases and the controls were almost the same for the total material. Case-control differences were found between the 11 sets with an interval of less than one year between drawing the sample and diagnosis of the cancer. The highest validity was found in CEA for colorectal cancer (specificity 91%; sensitivity 64%) and in CA 19–9 for stomach cancer (specificity 74%; sensitivity 73%). Conclusion — CEA, CA 19–9, CA 50, or TATI are not valid screening tests. Case-control differences were found with a potential one year screening interval, but they were not large enough for sufficient validity.

Background : Xenobiotic metabolizing enzymes (XMEs) are important detoxifiers of hazardous environmental agents, and their polymorphisms may therefore modify the risk of environmentally induced cancers. Consequently, the XME polymorphisms have been extensively studied in this context during recent years. Particular attention has been given to the polymorphisms of glutathione S -transferase (GST) M1, P1 and T1 genes. Previous studies have provided abundant data indicating these polymorphisms as important modifiers of individual susceptibility to cancers of environmental origin. It can be postulated that if the at-risk genotypes of these genes were real risk factors for the environmental cancers, their prevalence would presumably decrease with age in cancer-free part of the population. Methods : We tested the hypothesis in a population based group of 2105 Finns (1051 men, 1054 women) in five age strata (27, 37, 47, 57 and 67 years of age), all without clinically diagnosed cancer. Results : For GSTM1 genotype, a significant interaction was seen between gender and age among never smokers ( p =0.003). Currently smoking men tended to be less likely (OR 0.57, 95% CI 0.31–1.03), and currently smoking women more likely (OR 1.70, 95% CI 0.97–2.97) homozygotes for the GSTP1*B allele compared with never smokers. Moreover, the likelihood of being a concurrent carrier of the putatively protective genotypes of all of the three studied GST s was almost three-fold (OR 2.80, 95% CI 1.10–7.12) in heavy smokers in the two oldest age-groups compared with the other genotypes. Conclusions : Our findings based on a novel study design provide support to the previous case–control studies suggesting that GST genotypes modify individual risk of environmentally-induced cancers.

CYP2S1 is a recently discovered member of the cytochrome P450 ( CYP ) gene superfamily. Interestingly, even though the DNA sequence identifies it as the sole member of the new CYP2S family, CYP2S1 exhibits many features typical to CYP1 family members, e.g. dioxin-inducibility mediated by the aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, CYP2S1 metabolises some aromatic hydrocarbons as well as cellular substances. These characteristics, together with a wide extrahepatic tissue distribution, suggest that CYP2S1 may have an important role in both exogenous and endogenous metabolism. This is the first study characterising CYP2S1 alleles and naming them with the recommended CYP allele nomenclature. We used denaturing gradient gel electrophoresis (DGGE) and direct sequencing to investigate genetic variation of CYP2S1 in 100 male Finnish Caucasians. Those exons in which variation was found were examined in subsequent 100 subjects. The coding region of all of the nine exons, as well as a 449 bp fragment of the proximal promoter region, was analysed. This systematic investigation revealed eight single nucleotide polymorphisms (SNPs), which comprise nine different variant alleles (haplotypes), in addition to the wild-type allele. Seven of the SNPs occurred in the protein-coding areas and one in the proximal 3′ untranslated region (3′UTR). Two of these sequence variations (10347C > T and 13106C > T) result in non-conservative amino acid substitutions, i.e. Arg 380 Cys and Pro 466 Leu, respectively. The respective allelic variants, CYP2S1 * 2 ([10347C > T]) and CYP2S1 * 3 (13106C > T; 13255A > G]), occurred in our study population at frequencies of 0.50 and 3.75%, respectively. The most common of the variant alleles was CYP2S1 * 1H (23.8%), harbouring a 13255A > G substitution located in the 3′UTR.

Background The need for protecting agents against degenerative processes of the body has been proposed to be especially high in elderly people. In order to evaluate the prognostic value of various biochemical factors in ageing the associations of blood concentrations of several vitamins, mineral elements and some other suggested risk factors with vascular and non-vascular mortality were studied in an elderly population. Methods A large health survey with complete clinical evaluation was carried out in the City of Turku in 1982-1983. A random sample of 344 community-living elderly individuals aged 65 years or older, stratified into four age groups, was studied. During the 13 years follow-up 225 subjects had died. Calcium, magnesium, copper, ceruloplasmin, zinc, selenium, iron, ferritin, transferrin, alpha-tocopherol, retinol, folate, vitamin B12, malondialdehyde, orosomucoid and insulin levels were analysed from the blood specimens. The relations between the compounds measured and relative mortality risks during the 13-year follow-up were analysed by Cox proportional hazards model adjusting for other known risk factors. Results and conclusions High concentrations of serum copper, orosomucoid and insulin were associated with increased risk of vascular mortality. The relative risks within the subjects of the highest tertile of serum concentrations were 2.2 for copper, 1.8 for orosomucoid, and 1.8 for insulin when adjusted for many confounding risk factors. Low serum vitamin B12 concentrations appeared to be significantly (P = 0.01) associated with increased vascular mortality. The associations were essentially not more significant when adjusted only for age. Contrary to earlier observations concentrations of serum magnesium, selenium, alpha-tocopherol, iron and its binding proteins or plasma and erythrocyte folate were not associated with increased mortality risk when adjusted for confounding risk factors. The authors suggest that in elderly subjects these elements and compounds are at the most weak, and probably non-independent risk factors for vascular mortality.

Objective: We followed a group of 85 Finnish asbestosis patients radiographically for an average of 6.5 (range 2–10) years to examine the progression of the disease and to assess possible explanations for the progression. Methods: The examinations included full-size chest radiographs and a blood specimen analysis. The radiographs were classified according to the 1980 International Labor Office (ILO) classification. Progression was accepted if the second or third radiography was estimated (in a side-by-side comparison) to have more profusion of small opacities qualitatively than the first, even if the radiographs were classified into the same profusion category. Results: In all, 38% of the patients showed progression during the follow-up period. The average progression of small opacities ranged from ILO 1/1 to ILO 2/2 (0.4 minor ILO categories/year). The asbestosis was progressive more often among the sprayers than among the insulators and asbestos factory workers [cross-tabulation, odds ratio (OR) 5.0, 95% confidence interval (95% CI) 1.2–20]. In the logistic regression model the ILO classification category at the beginning of the follow-up (OR 1.54; 95% CI 0.96–2.47), the fibronectin (OR 1.01; 95% CI 1.00–1.01) and angiotensin-converting enzyme (ACE; OR 1.10; 95% CI 1.00–1.20) levels, and the erythrocyte sedimentation rate (ESR; OR 1.05; 95% CI 1.00–1.10) were statistically associated with the radiographic progression of small opacities. Abnormalities of the pleura were found to progress more often among the patients with progressive parenchymal opacities. Conclusion: For the progression of small-opacity profusion the significant predictors in the logistic regression model were the ILO profusion category at the beginning of the follow-up period, the fibronectin level, the ACE value, and the ESR. The model correctly classified 94% of the patients with progression and 65% of those without progression. The differences in the mean values recorded for the biomarkers between the progressors and nonprogressors, however, were small and may therefore not be of any importance to the clinician.

Background— Screening for ovarian cancer is based on ultrasound, colour Doppler, and tumour markers. There is only limited evidence on their discriminatory performance and no evidence on their effectiveness in reducing mortality. Objective— To investigate the discriminatory performance of CA 125 as a screening test for ovarian cancer. Methods— A registry of 15 093 serum samples drawn in 1968–72 was linked to the cancer registry. During follow up between 1968 and 1980 24 ovarian cancers were identified. One or two matched case—control design nested within the sample bank was applied and the concentrations of CA 125 were assessed. Results— Case—control differences (relative risk 4.0, 95% confidence interval 1.0 to 15.5 at 20kU/l) were found. Detection rate of the CA 125 test was 21–33% and the true negative rate was 75–98% depending on the cut off level and interval between drawing of the blood sample and diagnosis of the cancer. Conclusion— CA 125 is not a valid screening test if used alone. Case—control differences of borderline significance were found in CA 125 before diagnosis of ovarian cancer, but they were not large enough to provide a sufficient detection rate.

Fifty-year-old women (n = 519) attending a health examination were divided by their ovarian hormone status into four groups: premenopausal, perimenopausal, postmenopausal without ovarian hormone replacement therapy (HRT), and postmenopausal with HRT. Information on lifestyle factors was obtained with interviews and questionnaires. Bone mineral density at the calcaneus was assessed with single-photon absorptiometry, and several serum and urine markers of bone metabolism were measured. Postmenopausal women without HRT had significantly higher levels of fasting serum alkaline phosphatase, osteocalcin, total and ionized calcium, phosphate, and fasting urinary hydroxyproline than those in the three other study groups. No difference was found in bone mineral density between the premenopausal and postmenopausal groups. Postmenopausal women without HRT showed a marked correlation between serum osteocalcin and urine hydroxyproline. Both markers showed significant correlations with serum calcium, phosphate, and alkaline phosphatase. Multivariate analyses showed a statistically significant association of ovarian hormone status and body mass index with most measured markers of bone metabolism. The association between alcohol consumption and serum osteocalcin was highly significant. Cigarette smoking was associated with levels of serum alkaline phosphatase and total and ionized calcium. A weak association was found between coffee drinking and serum alkaline phosphatase.

The reference values for triglyceride concentrations in total serum and in its VLDL, LDL and HDL fractions have been produced based on the data obtained in the Mini-Finland Health Survey. The lipoprotein fractions were separated with ultracentrifugation. Efforts were made to obtain reference values for the healthy ambulatory population. Two health-derived selection criteria were used for inclusion of persons into the reference population: those based on the literature available and those based on the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, with minor modifications. The frequency distributions of triglycerides especially in total serum and in VLDL fraction were very skewed. Because of that the data were transformed before the calculation of the reference ranges according to the method of Box and Cox [1]. This transformation method appeared to be the best one of many tested methods in obtaining the distributions closer to the normal ones. The 95% inner reference intervals of total serum triglycerides in all subjects and in the two selection groups were 0.5-4.0, 0.5-2.8, and 0.5-3.2 mmol l-1 for men and 0.5-3.4, 0.5-2.3, and 0.5-2.4 mmol l-1 for women, respectively. The age dependence of triglyceride level was prominent in women after the early middle age. The distribution and age dependence of VLDL triglycerides resembled those of total triglycerides. In LDL and HDL fractions the skewness was not as clear as in the whole serum or in VLDL fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Background. There are no effective means for screening for lung cancer, so the authors assessed the utility of four lung cancer tumor markers for screening. Methods. A case–control study, nested in a cohort study based on the linkage of records of health survey examinees with Finnish Cancer Registry records, was used to test the validity of tumor markers carcinoembryonic antigen (CEA), tumor-associated trypsin inhibitor (TATI), neuron-specific enolase (NSE), and CA 50 in lung cancer screening. Ten years after health examinations, record linkage indicated that 187 men had lung cancer; 344 control subjects, matched for age, sex, and municipality were drawn from the same records. Results. The data allowed assessment of the sensitivity of the marker assays at a 95% specificity level, which was highest for CEA (17% at a concentration level of 5.3 μg/l). Logistic discrimination analysis indicated that of the other markers, only TATI, when used in combination, improved the discriminatory power of CEA. CEA and TATI levels correlated significantly with smoking. They also showed a significant gradient toward increasing risk of lung cancer from the lowest to the highest quintiles of marker levels (for CEA, crude relative risk between the highest and lowest quintiles, 8.6). The gradient also was evident in the subgroup whose cancer had been diagnosed more than 5 years after serum specimen collection. The trend persisted, although relative risk was halved after adjustment for smoking. Conclusions. The markers do not seem to be useful tools for lung cancer screening. However, CEA and TATI levels seem to give information on cancer risk long before the clinical cancer stage, as the quintile-based analyses of marker levels indicate.

All 636 cases of acute myeloid leukemia (AML) reported to the Finnish Cancer Registry between 1971 and 1977 inclusive were compared with patients with other forms of cancer (non-AML) from the same registry. We found no increasing trend in the incidence of AML for either sex, but we found some evidence for regional clusters in certain provinces of Finland. A statistically significant higher incidence was found for men than women in the age group of 50 to 80 years. Classification according to occupation at the time of diagnosis revealed no statistically significant differences between the leukemia cases and the patients with other forms of cancer, but forestry work was more common among the men with AML, and both health care and food industry work were more common among the women with AML. Classification for exposure to chemicals, solvents, or drugs did not yield any statistical differences. The results were inconclusive with regard to the possible role of occupational factors in the etiology of acute myeloid leukemia.

Simple direct dilution methods are described for the analysis of urinary chromium and nickel with electrothermal atomic absorption spectrometry. The day-to-day variation of the methods is in the order of 5%, and the detection limits 20 and 0.1 nmol/l (1.2 and 0.0052 micrograms/l) for urinary nickel and chromium, respectively. At levels corresponding to occupational exposures, both metals are stable (within 20%) in urine specimens in the refrigerator for the least ten months. The stability does not require acidification. Geometric mean values for urinary nickel and chromium in the non exposed population in Finland (n = 299 and 155) are 70 and 1.5 nmol/l (4.8 and 0.078 micrograms/l), and the upper 95% confidence limits from a log-normal distribution, are 170 and 11 nmol/l (10 and 0.57 micrograms/l), respectively.

The early biochemical and ultrastructural effects on the liver of CS2 administration in vivo to fasted rats were compared in animals treated and not treated with phenobarbital, to ascertain whether these effects differed quantitatively and/or qualitatively. Ultrastructural examination showed that in phenobarbital-treated rats, the main lesion induced by CS2 was an increase in the number and size of the lysosomes containing cell debris from other cell organelles such as mitochondria. The endoplasmic reticulum was unchanged compared to that of rats treated only with phenobarbital. In particular, there was no decrease in the rough endoplasmic reticulum. By contrast, in rats not treated with phenobarbital, the main effect of CS2 was a decrease in the number of ribosomes bound to the rough endoplasmic reticulum, with little or no change in other cell organelles. Cytochrome P-450 decreased more in phenobarbital-treated than in untreated rats, and cytochrome b5 decreased in phenobarbital-treated rats only. CS2 lowered aniline hydroxylase activity, expressed per nanomole of cytochrome P-450 in untreated rats, but increased this activity in phenobarbital-treated rats. The opposite was observed for microsomal peroxidase and cytosolic glutathione reductase activities. Liver catalase diminished more in phenobarbital-treated than in untreated rats. The effects of CS2 on liver endoplasmic reticulum as well as on the respective activities of aniline hydroxylase, microsomal peroxidase, and glutathione peroxidase show that untreated and phenobarbital-treated rats respond to CS2 administration in qualitatively different ways. It is suggested that in untreated rats, the effects observed are mainly due to CS2 itself, whereas in phenobarbital-treated animals, the effects are mainly caused by reactive CS2 metabolites formed by the mixed function oxidase microsomal system.

It is well known that phenobarbital treatment increases the production of superoxide anion by liver microsomes. Since the toxicity of superoxide anion and of its product, hydrogen peroxide, is well documented we measured the activities of the liver enzymes which protect the cell against the reduced forms of oxygen and the microsomal content of lipoperoxides in phenobarbital-treated rats. It was found that no lipoperoxides accumulate in the microsomes and that glutathione peroxidase, glutathione reductase activities, and the peroxidative activity of cytochrome P-450 were increased while catalase and superoxide dismutase activities were not modified.

The reference values for gamma-glutamyltransferase (GT), aspartate aminotransferase (ASAT) and alkaline phosphatase (AFOS) activities in serum have been produced on the basis of measurements done in the Mini-Finland Health Survey. A representative sample of all Finns aged 30 years or over comprised 8000 persons, of whom 99.2% participated in the actual health survey. Every effort was made to obtain reference values for the healthy ambulatory population. Three separate health-derived selection criteria were used to obtain such reference values for the above-mentioned enzymes: those based on the available literature, with minor modifications, the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, criteria that were obtained after subgroup comparisons of the obtained data, where all the factors affecting the enzyme levels were identified. The recommendations of the Expert Panel on Theory of Reference Values (1987) were strictly adhered to in the statistical analyses. The distribution of the serum activity of GT was very skewed. The overall intervals for men and women were 5.1-1460 and 4.7-748 U/l, respectively. The frequency distributions could be transformed to the normal ones logarithmically. The 95% inner reference intervals for GT in the three groups were 7-76, 7-65, and 8-57 U/l for men and 6-35, 6-30 and 6-32 U/l for women, respectively. For ASAT the full intervals of the enzyme levels in serum were 2.6-770 U/l for men and 8.3-172 U/l for women. After logarithmic transformation the respective reference intervals in the three selection groups were 14-42, 14-40 and 13-39 U/l for men and 13-33, 12-31 and 13-33 U/l for women. The full intervals of AFOS were 47.5-2755 and 5.4-816 U/l for men and women, respectively; after the logarithmic transformation the reference intervals of the three selection groups were 98-267, 97-254 and 97-264 U/l for men and 77-265, 75-231 and 75-250 U/l for women, respectively.

Wollastonite metasilicate fibers are rather similar in form, length, and diameter, but mineralogically different, to amphibole asbestos fibers. We have studied immunologic findings from 46 men exposed to wollastonite at a limestone quarry for at least 10 years. These workers showed a higher prevalence of positive serum rheumatoid factors than blood donors did. This finding resembles the one detected among asbestos workers. The group of wollastonite workers with radiological signs of pulmonary fibrosis had activities of serum angiotensin-converting enzyme that were similar to those of wollastonite workers without fibrosis. A mortality study of 238 quarry workers with 5,769 person-years was, as expected, nonpositive. It was interesting that one woman with 20 years of exposure to wollastonite and with no other known exposure to fibers revealed a malignant retroperitoneal mesenchymal tumor 30 years after the initial exposure. This kind of very rare tumor is difficult to distinguish from mesothelioma. However, this is only one case, and it is impossible to draw any definite conclusions.

In vivo administration of carbon disulfide to fasted rats leads to the disappearance of 35% of liver microsomal P -450 hemoproteins measured by the CO-binding spectrum of dithionite-reduced microsomes. P -450 hemoprotein disappearance is not accompanied by any change in the other components of P -450 monooxygenase systems (i.e., cytochrome P -420, cytochrome b 5 and NAD(P)H reductases). The spectrophotometrically remaining P -450 hemoproteins after carbon disulfide administration have increased peroxidase activity, increased apparent K S and A max for hexobarbital and aniline bindings, and decreased aniline hydroxylase activity. The lower wavelength peak of pyridine binding is increased whereas the higher wavelength peak of the binding is decreased at all pH values used. The mechanism by which CS 2 leads to these effects is suggested to be an alteration of a CS 2 -sensitive population of liver P -450 hemoproteins. This, however, remains to be demonstrated.