Inulin results in increased levels of beta-catenin and cyclin D1 as the adenomas increase in size from small to large in the Min/+ mouse

The mechanism that drives the growth of some colonic adenomas towards malignancy, while permitting others to remain for decades in quiescence, remains unknown. Diets can alter the growth rate of intestinal tumours but it is still unknown whether diets are able to alter the molecular biology of these adenomas in a way that predicts further outcome. To address this issue we fed Min/+ mice with two diets known to lead to different adenoma outcomes: a high-fat control diet (n 15) or a high-fat inulin-enriched (10 % w/w) diet (n 13). To study the effect of diet on cell signalling during adenoma growth, the adenomas of each Min/+ mouse were divided into three size-categories, and the levels of beta-catenin, E-cadherin, cyclin D1 and matrix metalloproteinase-9, which are known to be involved in colon tumorigenesis, were determined. The growth-promoting inulin diet resulted in more large adenomas than the control feeding (P = 0.003) and doubled the total area of the adenomas (P = 0.008). The inulin diet increased the expression of nuclear beta-catenin (P = 0.004) and its target cyclin D1 (P = 0.017) as the adenomas increased in size from small to large, indicating the presence of an accelerated cancerous process. Neither phenomenon was seen in the control group during adenoma growth. Our results suggest that in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should also be considered when evaluating preventive dietary strategies.     

Lack of effect on blood pressure by polyunsaturated and monounsaturated fat diets.

We carried out a blind highly controlled study to investigate the effects of a sunflower-oil-rich diet and a rapeseed-oil-rich diet on the blood pressure of normotensive subjects. Twenty-nine men and 30 women, average age 30 years (range 18-65) were first fed a baseline diet high in saturated fatty acids (19 E% (percentage of total energy), total fat 36 E%) for 2 weeks. According to the crossover design 30 subjects then received a sunflower oil diet high in polyunsaturated fatty acids (13 E%, total fat 38 E%) followed by a low erucic acid rapeseed oil diet high in monounsaturated fatty acids (16 E%, total fat 38 E%) for 3.5 weeks each. The other 29 subjects had the same diets in reverse order. At the end of the saturated fat period systolic blood pressure was 122.6 +/- 11.5(mean +/- SD) mmHg and diastolic blood pressure 75.4 +/- 7.5 mmHg; during the sunflower oil diet the figures were 119.6 +/- 10.3 and 73.9 +/- 7.4 mmHg, and during the rapeseed oil diet 120.1 +/- 11.2 and 72.6 +/- 6.4 mmHg, respectively. There was a significant difference in diastolic blood pressure only between the two oil diets (P less than 0.01). At the end of a 4 weeks' recovery period the systolic and diastolic blood pressures of the subjects were even lower (118.6 +/- 10.6 and 72.3 +/- 8.3 mmHg, respectively) than during the study. These results suggest that the dietary changes had only minor effects - if any at all - on blood pressure in healthy normotensive subjects.     

Selenium-iron interaction in young women with low selenium status

The effect of inorganic selenium (Se) supplementation on iron status and iron supplementation on selenium status was investigated in Finnish female students (=33). The students were divided into three groups and supplemented daily for four weeks either with 150 μg Se as sodium selenate, or 120 mg Fe as ferrous sulfate, or 120 mg Fe as ferrous sulfate and 150 μg Se as sodium selenate. Plasma selenium level was used as an indicator of body selenium status. Haematocrit and serum ferritin concentrations were measured to determine the changes in body iron status. The initial plasma selenium level of all subjects was 74.7 ± 2.9 ng/ml (mean ± SEM). The increase in the plasma Se level in the group receiving sodium selenate was significantly higher (P<0.05) than in the group having both sodium selenate and ferrous sulphate. The plasma selenium level in the group receiving ferrous sulphate decreased from 76.0 ± 2.8 ng/ml to 67.8 ± 2.3 (P<0.05) during the supplementation period, but returned to the initial level four weeks after the end of iron supplementation. The data indicate that the supplementary iron affected adversely the body selenium status of these subjects. On the other hand, Se supplementation had no effect on body iron status as indicated by the serum ferritin and haematocrit levels. It was also shown that there was no obvious interaction between the normal levels of selenium and iron in the body, since no correlations were found between plasma selenium and serum ferritin (r = 0.30, P>0.05) in the beginning of the study.     

Breast cancer and occupational exposures in women in Finland.

BACKGROUND: The etiology of breast cancer is not fully understood. Environmental and occupational exposures may contribute to breast cancer risk. METHODS: We linked 324 job titles from the 1970 census of 892,591 Finnish women with incidence of breast cancer (23,638 cases) during 1971-1995. We converted job titles to 31 chemical and two ergonomic agents through a measurement-based, period-specific, national job-exposure matrix. Poisson regression models were fit to the data, with adjustment for birth cohort, follow-up period, socioeconomic status, mean number of children, mean age at first delivery, and turnover rate. RESULTS: For premenopausal breast cancer, medium/high level of occupational exposure to ionizing radiation was associated with a standardized incidence ratio (SIR) of 1.3 (95% confidence interval (CI) 0.7-2.5; trend P = 0.03). For postmenopausal breast cancer, we found on SIR of 1.2 (1.1-1.3) for low level and 1.4 (1.1-1.8) for medium/high level of ionizing radiation (trend P = 0.001); and an SIR 1.3 (1.1-1.7) for medium/high levels of both asbestos and man-made vitreous fibers. Aromatic hydrocarbon solvents showed a significant trend for a modest excess of postmenopausal breast cancer. CONCLUSIONS: Our study indicates that occupational exposure to ionizing radiation may be associated with an increased risk of female breast cancer. High-quality studies on environmental and occupational etiology of breast cancer are needed for further elucidation of risk factors.     

How consistently distributed are the socioeconomic differences in severe back morbidity by age and gender? A population based study of hospitalisation among Finnish employees

Aims

To study the socioeconomic distribution of severe back morbidity by age and gender, and to examine to what extent the differences in back morbidity between socioeconomic groups are particularly related to manual work in different age groups.

Methods

Hospital admissions in 1996 for back disorders of 25–64 year old men (3123 of a total 743 961) and women (3043 of 773 936) from the Finnish Hospital Discharge Register were linked with demographic and socioeconomic data from the 1995 population census. Poisson regression analysis was used to calculate the rate ratios for back related hospitalisation by occupational class and education. The distribution of cases according to occupational status and education was presented in relation to the whole occupationally active workforce by age and gender.

Results

Blue‐collar (manual) workers had a higher risk of being hospitalised because of back disorders compared with white‐collar employees (non‐manual) in all age groups among both genders. Manual work versus non‐manual work was associated with a 1.3 to 1.4‐fold risk (95% CI 1.0 to 1.8) among women and a 1.3 to 1.6‐fold risk (95% CI 1.1 to 2.2) among men. The risk of hospitalisation was further inversely associated with educational level within manual and non‐manual work in all other age groups except in those aged 55–64 years. Gender related differences were much smaller compared with the socioeconomic ones.

Conclusions

Socioeconomic differences in back morbidity leading to hospitalisation were consistent by age and gender. The results suggest that not only the physical strenuousness of work, but also other causes of severe back disorders are clustered around a subject''s socioeconomic status, indicated by formal education. This may have implications for prevention and the planning of rehabilitation.     

Inhalation exposure to 1,3-butadiene and styrene in styrene-butadiene copolymer production

This study assessed personal exposure to 1,3-butadiene (BD) and styrene in three plants manufacturing styrene-butadiene (SB) copolymers. Air samples were collected from the breathing zone of 28 workers over 4 months in three SB plants using diffusive samplers. The total number of samples was 885 with the number of samples per participant varying from 19 to 39. Samples were collected by use of 3M 3500 passive monitors and analyzed with a gas chromatograph (GC). Sampling proved to be simple and inexpensive and laboratory analysis of BD could detect 0.01 and 0.007 part per millions (ppm) of styrene in the 8h samples. In the case of BD, 624 samples were below the limit of quantification (LOQ), 240 samples were between the LOQ and 1 ppm, and 21 samples exceeded the threshold limit value (TLV). In the case of styrene 336 samples were below the LOQ, 548 samples were between the LOQ and 20 ppm. The TLV was exceeded once. The data gives a comprehensive picture of personal exposure of workers in modern SB latex manufacturing plants. The study illustrates also how the new TLV of BD is being implemented.     

Nuclear factor kappaB is downregulated and correlates with p53 in the Min mouse mucosa during an accelerated tumor growth

The nuclear factor kappaB signaling pathway has gained attention for its role in the carcinogenic process. We have measured the protein levels of the p65 subunit during a growth of adenomas in the Min mouse model for colon cancer. To study how an accelerated growth of adenomas affect cell signalling, adenoma growth was increased by an inulin diet (10%) that we have shown previously to be a promotor of adenoma formation. In our study, the association between NF-kappaB, p53, beta-catenin, Fas and COX-2 were evaluated by measuring their protein levels in 9- and 15-week old Min mouse adenomas and surrounding mucosa. The amount of p65 rouse between 9- and 15-weeks in the mucosa of the control-fed mice (p = 0.032). The inulin-fed mice had less p65 in the nucleus of the mucosa at 15 weeks of age compared to the control (p = 0.064), although the adenomas were significantly larger (1.46 mm +/- 0.12 for inulin, 0.97 mm +/- 0.12 for control, p < 0.001). Nuclear p65 correlated positively with nuclear p53 in the mucosa (p < 0.001) and adenoma (p < 0.001) tissues. Also, p65 correlated positively with nuclear beta-catenin in the mucosa (p = 0.012) and the adenoma (p = 0.001). Fas expression increased in the inulin group between 9-15 weeks (p = 0.034) and correlated negatively with p65 (p = 0.03). The amount of COX-2 in the adenoma tissue increased between 9-15 weeks and did not correlate with p65. The results suggest that p65 is involved in a p53-dependent apoptotic response in the Min mouse.     

The plant lignans matairesinol and secoisolariciresinol administered to Min mice do not protect against intestinal tumor formation

The lignans matairesinol (MAT) and secoisolariciresinol (SECO) were fed to Min mice at 0.02% (w/w) in diet to study their effects on intestinal tumor development. The mean number (67 vs. 51, P=0.052) and size (1.4 vs. 1.2 mm, P=0.011) of tumors in the MAT group was elevated when compared with the control group. Tumor formation of the SECO group did not differ from the control group. Intake of MAT increased the level of both MAT and enterolactone in the plasma while SECO feeding increased SECO, enterodiol, and enterolactone (P=0.001). These results showed that MAT or SECO do not prevent intestinal carcinogenesis in Min mice and that MAT may have adverse effects.