Genetic metabolic polymorphisms and the risk of cancer: a review of the literature

The purpose of this paper is to systematically analyse the design and results of epidemiological studies on the association between various types of cancer (lung, bladder, breast, colon, stomach) and four genetically-based metabolic polymorphisms, involved in the metabolism of several carcinogens (glutathione-S-transferase M1, debrisoquine hydroxylase, N acetyltransferase, aryl hydrocarbon hydroxylase). These inherited polymorphisms usually cause modifications in the quality or quantity of the relevant enzymes. Such enzymes are involved in the activation/inactivation of known carcinogens and seem to modify the extent to which carcinogens interact with DNA in target tissues. Two enzymes, debrisoquine hydroxylase and aryl hydrocarbon hydroxylase, activate procarcinogens to carcinogens (phase I enzymes). The other two, glutathione-S-transferase M1 and N-acetyltransferase, mainly detoxity carcinogenic substances (phase II enzymes). Because of their role as host factors (modulating the action of carcinogens), it has been hypothesized that subjects presenting a specific phenotype for such polymorphisms could be at a greater risk of developing various types of cancer. A number of epidemiological studies have investigated such associations, often with discordant results. We examine and discuss the design of the studies, and present a meta-analysis of the available data.     

A Major Gene for Resting Metabolic Rate Unassociated with Body Composition: Results from the Québec Family Study

A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat-free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal — i.e., there was evidence for either a major gene or a multifactorial component (i.e., polygenic and/or familial environment). The multifactorial model was preferred over the major gene model, although the latter did segregate according to Mendelian expectations. However, after the effects of FM and FFM were accounted for, a major gene effect was unambiguous and compelling. The putative locus accounted for 57% of the variance, affected 7% of the sample, and led to high values of RMR. The lack of a significant multifactorial effect suggested that the familial etiology of RMR adjusted for FM and FFM was likely to be entirely a function of the major locus. Comparing the RMR results from pre- and post-adjustment for FM and FFM suggests a plausible hypothesis. We know from earlier studies in this sample that there is a putative major gene for FM and a major non-Mendelian effect for FFM. The current study leads us to speculate that: (1) the gene(s) affecting body size and body composition also may have an effect on RMR, and further (2) removal of the effect of the major gene(s) for body size and composition allowed for detection of an additional major gene affecting only the RMR. Thus, RMR appears to be an oligogenic trait.     

Life history and species composition of the damselfly assemblage along the urban tract of a river in central Italy

The species composition of the damselfly assemblage and the life history patterns of two Coenagrionidae (Ischnura elegans and Cercion lindeni) were investigated along the urban tract of a river characterized by increasing organic pollution. The assemblage was dominated by generalist species, usually recorded in lentic habitats, rather than by typical riverine species and the proportion of the latter decrease at the most polluted sites. At the end of Winter, the mean size and in star distribution were different between the sampling sites showing that the life history of both species examined were influenced by a degradation of the environmental quality. A longer reproductive period, absence of diapause, and tolerance of low oxygen concentration appear to be key factors that allow generalist species I. elegans and C. lindeni to predominate at the polluted sites. This revised version was published online in August 2006 with corrections to the Cover Date.     

Decreased lipolysis in peanuts by a pyridazinone bioregulator

Peanut,Arachis hypogaea, plants were treated in the field with the bioregulator BAS 105 00W, 4-chloro-5-dimethylamino-2-phenylpyridazin-3-one, a substituted pyridazinone, at different times of development. The seeds were harvested, dried, hand-shelled, and analyzed for lipoxygenase activity and conjugated diene hydroperoxide content. Reduced lipoxygenase activity occurred when the bioregulator was applied to the plants at flowering and pegging. The conjugated diene hydroperoxide content decreased the most in peanuts when the bioregulator was applied at pegging. The apparent K_m for lipoxygenase of treated peanuts with linoleic acid as substrate was the same as that for untreated peanuts.     

Studies on the molecular basis of H+ translocation by cytochromec oxidase

We report here studies which characterize further the interaction ofN,N-dicyclohexylcarbodiimide with cytochromec oxidase leading to inhibition of H⁺ translocation by the enzyme. Further evidence is presented to show that the inhibition results from a real interaction of DCCD with the enzyme and cannot be accounted for by uncoupling and, contrary to recent criticisms, this interaction occurs specifically with subunit III of the enzyme even at relatively high inhibitor-to-enzyme stoichiometries. Use of a spin-label analogue of DCCD has enabled us to demonstrate that the carbodiimide-binding site is highly apolar and may not lie on the pathway of electron transfer.Abbreviations DCCD N,N-dicyclohexylcarbodiimide - NCCD N-(2, 2, 6, 6-tetramethylpiperidyl-1-oxyl)-N-(cyclohexyl)carbodiimide - Hepes 2-(N-2-hydroxyethylpiperazin-N-yl) ethane sulfonate - TMPD N,N,N,N-tetramethylphenylenediamine