An intact episomal E2 gene is present in most cases of these cervical cancers, and could therefore replace the regulatory function of an integrated defective E2 gene.
A working group was established to evaluate the need for iodine enrichment in Denmark. Judged from studies of urinary iodine excretion and one dietary survey the intake of iodine in Denmark is low compared with recommended intakes. The occurrence of non-toxic goitre is relatively high; between 9 and 13% in elderly women. Furthermore, a high occurrence of toxic goitre has been seen in the western part of Denmark. On the other hand, an increased or a high intake of iodine may lead to hyperthyroidism and thyroiditis. The working group concluded that an increase in iodine intake in the Danish population is needed and the best way to achieve this is to iodize all salt. To avoid side effects of a sudden large increase in iodine intake the initial amount of iodine in salt will only be 2 ppm.
The human malignant B-lymphocyte cell lines Reh and U698 show arrest in G 2 phase after ionizing radiation (IR), but only Reh cells arrest in G 1 phase and die by apoptosis. We have used cDNA microarrays to measure changes in gene expression at 2, 4 and 6 hr after irradiation of Reh and U698 cells with 0.5 and 4 Gy in order to begin exploring the molecular mechanisms underlying the phenotypic changes. We also investigated whether gene expression changes could be caused by possible aberrations of genes, as measured by comparative genomic hybridization. Reh cells showed upregulation of CDKN1A that likely mediated the G 1 arrest. In contrast, U698 cells have impaired function of TP53 protein and no activation of CDKN1A, suppressing the arrest in G 1 . The G 2 arrest in both cell lines was likely due to repression of PLK1 and/or CCNF. IR-induced apoptosis in Reh cells was probably mediated by TP53 and CDKN1A, whereas a high expression level of MCL1, caused by gene amplification, and activation of the NFKB pathway may have suppressed the apoptotic response in U698 cells. Genes suggested to be involved in apoptosis were activated long before this phenotype was detectable and showed the same temporal expression profiles as genes involved in cell cycle arrest. Our results suggest that differences in functionality and/or copy number of several genes involved in IR-regulated pathways contributed to the phenotypic differences between Reh and U698 cells after IR, and that multiple molecular factors control the radiation response of malignant B lymphocytes. ' 2005 Wiley-Liss, Inc.
The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACF). Male Wistar rats were initiated with oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 or 20 weeks. Throughout the study the animals were fed 1) semisynthetic casein-based control diet, 2) control diet with 20% lard, 3) control diet with 20% lard and 20% dietary fiber, or 4) control diet where most of the carbohydrate pool was substituted with sucrose and dextrin. The composition of the different diets was designed to achieve equivalent intakes of essential nutrients. Animals were killed after 10, 20 and 31 weeks. The study showed a pronounced effect of dietary composition on the development of DMH-induced ACF. The diet high in sucrose and dextrin caused a statistically significant increase (p < or = 0.05) in the total number of ACF and number of small and medium ACF. Adding lard to the standard diet did not cause an increase in ACF, but if the dietary fiber was added to the high-fat diet, a statistically significant reduction (p < or = 0.05) in the total number of ACF and number of small and medium ACF was observed. The values of large and extra-large foci reflected the same effect of diets on ACF. The results indicate that tumors in the group fed the diet high in refined carbohydrates were more prominent and occurred with a higher incidence. However, the difference is based on few tumors and is not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Formation of aberrant crypt foci (ACF) in archived colon tissue from animals in a previous study was examined. The animals were fed a semisynthetic casein-based diet in which the carbohydrate pool was substituted with a dietary beet fiber (Fibeta) as the only source of fiber. Oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 weeks were used as initiator. The rats were fed different levels of the fiber in a preinitiation period, during initiation, or in a postinitiation period. In general, the results showed a statistically significant inverse relation between duration of intake of high-fiber diet and number of animals with ACF, as well as the total number of ACF and number of small ACF (1-3 crypts) per affected animal. The previously reported data showed no protective effect of the dietary fiber at any stage of the colorectal carcinogenic process. The lack of correlation between the outcome of ACF and tumors could be related to the observation that statistically significant differences between groups were seen only in the total number of ACF and number of small ACF. The hypothesis that ACF are preneoplastic lesions needs to be supported by further experimental data. The present state of knowledge could indicate that ACF represent true preneoplastic lesions progressing into colon tumors or that ACF and colon tumors represent two parallel independent events as a consequence of the cancer initiation (i.e., the ACF not being preneoplastic lesions per se).
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