Does Helicobacter pylori cause gastric cancer via oxidative stress?

Epidemiologic evidence strongly supports a causal role for Helicobacter pylori in gastric carcinogenesis. The infection was recognized as a Class I human carcinogen by the International Agency for Research on Cancer in 1994. The bacterium does not induce carcinogenesis by itself. The present scientific consensus is that the bacterial oncogenic role is mediated by the chronic active inflammation it elicits in the gastric mucosa. Although the ultimate basic mechanism of carcinogenesis is unknown, strongly suggestive evidence points to oxidative stress as having a pivotal role in the process. This review discusses some of the evidence accumulated so far to support such a role. Numerous avenues of research are open and represent an intriguing challenge to the scientific community.     

Do mycoplasmas cause human cancer?

A linkage between mycoplasmas and malignancy was mainly proposed in the 1960s when human-associated mycoplasmas were becoming of interest given the novel characterization of the human respiratory pathogen Mycoplasma pneumoniae. Associations with leukemia and other malignancies, however, were largely ascribed to tissue-culture contamination, which is now recognized as a significant potential problem in molecular biology circles. A few epidemiological studies, however, continue to raise concern over such a linkage. As well, in vitro data have demonstrated the potential for some mycoplasmas to induce karyotypic changes and malignant transformation during chronic tissue-culture infestation. As cellular and molecular mechanisms for such transformation become studied, a resurgence of interest in this area is inevitable. A role for mycoplasmas in malignancy of any sort is conjectural, but there remains a need to continue with focussed epidemiological and laboratory investigations.     

Does streptomycin cause an error catastrophe?

We have examined the interpretation that streptomycin kills a bacterial culture by initiating the so-called error catastrophe. In particular, we asked whether the increased translational error rate induced by the antibiotic gives rise to an autocatalytic loss of functional fidelity of the devices responsible for gene expression, which ultimately causes the death of the culture. We have analyzed the performance characteristics of one of these devices, namely the ribosome in streptomycin-treated bacteria. We find that, although the treated ribosomes are constructed from error-containing proteins, they are not significantly different in elongation rate and fidelity from those ribosomes taken from untreated bacteria. We conclude that the bacteriocidal effect of streptomycin is not due to the initiation of an error catastrophe.     

Does human oocyte cryopreservation affect equally on embryo chromosome aneuploidy?

Oocytes cryopreservation as an important part of assisted reproductive technologies, which should ensure after warming not only intact oocyte morphological characteristics, but also their genetic apparatus stability. However, the meiotic spindle is very sensitive to the temperature fluctuations that can lead to unequal chromosome segregation during meiosis and as a consequence can cause embryo aneuploidy after oocyte fertilization. The aim of the study was to estimate the oocytes cryopreservation impact on human embryo chromosome aneuploidy. It has been shown that fertilization rate of the cryopreserved oocytes did not differ from fresh ones (83.1% vs 84% respectively). The number of blastocysts obtained from cryopreserved oocytes was less than that obtained from fresh oocytes, however, their morphological characteristics were better if compared the fresh oocytes. Our results showed different cryopreservation impact on aneuploidy rates of certain chromosomes in embryos obtained from cryopreserved oocytes. They had an increased aneuploidy of chromosome 13 and a decreased nondisjunction of chromosome 18 and sex chromosomes.     

Do oestrogens induce chromosome specific aneuploidy in vitro, similar to the pattern of aneuploidy seen in breast cancer?

The study was concerned with investigating the specific effects of non-DNA reactive oestrogens at low "biologically relevant" doses and the causative role they may play in breast cancer through inducing aneuploidy. A review of previous studies identified a non-random pattern of aneuploidy seen in breast cancers. This information was used to select those chromosomes that undergo copy number changes in breast cancer and chromosomes that appear stable. A panel of centromeric specific probes were selected and centromeric specific fluorescence in situ hybridisation (FISH) was carried out on the human lymphoblastoid cell line, AHH-1, which had been pre-treated with the chemical aneugens 17-beta oestradiol, diethylstilbestrol (DES) and bisphenol-A (BP-A). The results suggest that oestrogens may play a causative role in breast cancer by inducing a specific pattern of aneuploidy similar to that seen in breast carcinomas. 17-beta oestradiol appears to induce changes most similar to those seen in breast tumours, BP-A induces the same pattern but at a lower frequency and DES appears to be less chromosome specific in its act.     

Does the cryogenic freezing process cause shorter telomeres?

We have observed evidence of increased telomere shortening in short-term T-lymphocyte cultures following freezing and thawing of the original inoculum obtained by ficoll-paque gradient centrifugation, compared to T-lymphocytes that were cultured immediately without freezing and thawing from the same blood sample from 3 female and 3 male adults. Because freezing may have similar effects on other cell types, and because telomere shortening may only manifest its effects after many years or decades, we suggest there is a pressing need for evaluation of the effects of freezing on any cells envisioned for clinical applications, including embryo implantation.     

Does physical inactivity cause nonalcoholic fatty liver disease?

While physical activity represents a key element in the prevention and management of many chronic diseases, we and others believe that physical inactivity is a primary cause of obesity and associated metabolic disorders. Unfortunately, accumulating evidence suggests that we have engineered physical activity out of our normal daily living activity. One such consequence of our sedentary and excessive lifestyle is nonalcoholic fatty liver disease (NAFLD), which is now considered the most common cause of chronic liver disease in Westernized societies. In this review, we will present evidence that physical inactivity, low aerobic fitness, and overnutrition, either separately or in combination, are an underlying cause of NAFLD.     

Maternal-age effect in aneuploidy: Does altered embryonic selection play a role?

The age of mothers of children with trisomy 21 (47,+21) is elevated no matter if the extra chromosome is of maternal or paternal origin, and it has been postulated that decreasing maternal selection against affected conceptuses with advancing age might explain this observation. Since the absence of sufficient data on 47,+21 abortuses precludes a direct test of this hypothesis, we have taken an indirect approach. Pooled data from spontaneous abortions and live births with autosomal trisomies, XXY and XXX, were examined to determine the natural history of these aneuploid conceptuses and its relation to maternal age. The results are consistent with decreasing embryonic selection in older women.     

Guilt by association? p53 and the development of aneuploidy in cancer

Aneuploidy is one of the most frequent genetic alterations in solid tumors. It is commonly caused by cell division errors that are induced by oncogene activation or loss of tumor suppressor functions. In addition, certain viral oncoproteins have been implicated in the induction of chromosome copy number changes. Aneuploidy and inactivation of p53 frequently coincide in human cancers but there is increasing evidence that loss of p53 by itself is not a primary cause of aneuploidy. Nonetheless, p53 inactivation synergizes with additional oncogenic events to promote aneuploidy and may facilitate chromosomal imbalances through indirect mechanisms. This review summarizes the current knowledge about the association between aneuploidy and p53, and discusses two of the most controversial mechanisms that have been implicated in genomic instability associated with loss of p53: subversion of ploidy control and aberrant centrosome duplication.     

Does forest fragmentation cause an increase in forest temperature?

Forest fragmentation is considered by many to be a primary cause of the current biodiversity crisis. The underlying mechanisms are poorly known, but a potentially important one is associated with altered thermal conditions within the remaining forest patches, especially at forest edges. Yet, large uncertainty remains about the effect of fragmentation on forest temperature, as it is unclear whether temperature decreases from forest edge to forest interior, and whether this local gradient scales up to an effect of fragmentation (landscape attribute) on temperature. We calculated the effect size (correlation coefficient) of distance from forest edge on air temperature, and tested for differences among forest types surrounded by different matrices using meta-analysis techniques. We found a negative edge-interior temperature gradient, but correlation coefficients were highly variable, and significant only for temperate and tropical forests surrounded by a highly contrasting open matrix. Nevertheless, it is unclear if these local-scale changes in temperature can be scaled up to an effect of fragmentation on temperature. Although it may be valid when considering “fragmentation” as forest loss only, the landscape-scale inference is not so clear when we consider the second aspect of fragmentation, where a given amount of forest is divided into a large number of small patches (fragmentation per se). Therefore, care is needed when assuming that fragmentation changes forest temperature, as thermal changes at forest edges depend on forest type and matrix composition, and it is still uncertain if this local gradient can be scaled up to the landscape.     

Aurora kinases, aneuploidy and cancer, a coincidence or a real link?

As Aurora kinases are overexpressed in a large number of cancers, and ectopic expression of Aurora generates polyploid cells containing multiple centrosomes, it has been tempting to suggest that Aurora overexpression provokes genetic instability underlying the tumorigenesis. However, examination of the evidence suggests a more complex relationship. Overexpression of Aurora-A readily transforms rat-1 and NIH3T3 cells, but not primary cells, whereas overexpression of Aurora-B induces metastasis after implantation of tumors in nude mice. Why do polyploid cells containing abnormal centrosome numbers induced by Aurora not get eliminated at cell-cycle checkpoints? Does this phenotype determine the origin of cancer or does it only promote tumor progression? Would drugs against Aurora family members be of any help for cancer treatment? These and related questions are addressed in this review (which is part of the Chromosome Segregation and Aneuploidy series).