D and C Red No. 9: Genotoxic or non-genotoxic carcinogen?

The azo-compound, D and C Red No. 9 was assayed for genotoxicity in vivo using the rat micronucleus test and the rat ex vivo liver UDS assay. Uniformly negative results were obtained in both assays, even though large oral doses were used (2 g/kg). These results suggest that the tumorigenic effects of this compound in rats are mediated through a non-genotoxic rather than a genotoxic mechanism. Further experiments using additional end-points such as ³²ap-post-labelling would further substantiate this conclusion     

Glucose-induced effects and joker function of glucose: endocrine or genotoxic prevalence?

The steady increase in chronic "glycemic load" is characteristic for modern times. Among myriad of glucose functions, two principals can be emphasized: first, endocrine (in particular, ability to induce insulin secretion) and second, DNA-damaging related to formation of reactive oxygen species (ROS). It was suggested by us earlier that a shift in the ratio of mentioned functions reflects a possible "joker" role of glucose as an important modifier of human pathology. Therefore, we embarked on a study to investigate an individual effect of peroral glucose challenge on serum insulin level and ROS generation by mononuclears (luminol-dependent/latex-induced chemiluminescence) in 20 healthy people aged between 28-75. Concentrations of glucose, blood lipids, carbonylated proteins, malondialdehyde, leptin and TNF-alpha were determined as well. On the basis of received data two separate groups could be distinguished: one (n=8), in which glucose stimulation of ROS generation by mononuclears was increased and relatively prevailed over induction of insulin secretion (state of the so called glucose-induced genotoxicity, GIGT), and another (n=12), in which signs of GIGT were not revealed. People who belonged to the first group were characterized with a tendency to lower body mass index, blood leptin and cholesterol and to higher TNF-alpha concentration. Thus, if joker function of glucose is realized in "genotoxic mode", the phenotype (and probably genotype) of subjects may be rather distinctive to the one discovered in glucose-induced "endocrine prevalence". Whether such changes may serve as a pro-mutagenic or pro-endocrine basis for the rise of different chronic diseases or, rather, different features/aggressiveness of the same disease warrants further study.     

Oxidative DNA damage — The effects of certain genotoxic and operationally non-genotoxic carcinogens

A wide variety of oxidative DNA lesions are commonly present in untreated human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to lead to base mispairing (mutation) on DNA replication. Other lesions remain to be investigated in this respect. Oxidative DNA lesions on cell replication may, in appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA damage, on fixation, may also lead to cytotoxicity followed by regenerative proliferation. The probable or possible importance of oxidative DNA damage is reviewed for various classes of carcinogens and natural processes, including metal ions, high-energy radiation, miscellaneous chemicals, tumor-promoting agents, polyhydroxyphenols/quinones, lipid metabolism, peroxisome proliferators and thyroid function. It is concluded that although the evidence needs considerable strengthening in many of these examples, the available information indicates the potential importance of oxidative DNA damage in the induction of tumors by these agents. It is also possible that non-cancerous degenerative diseases associated with aging are the result of the accumulation of lesions resulting from unrepaired oxidative DNA damage.     

C. difficile ribotype 027 or 176?

Clostridium difficile is a major nosocomial pathogen of present times. The analysis of 624 C. difficile strains from 11 hospitals in the Czech Republic in 2013 revealed that 40 % of isolates belonged to ribotype 176. These results suggest that the incidence of CDI (C. difficile infection) in the Czech Republic has increased probably in connection with C. difficile ribotype 176. The molecular systems Xpert C. difficile Epi assay (Cepheid Inc., Sunnyvale, CA) diagnoses toxigenic strains and supports C. difficile ribotype 027 determination based on three specific target places in the toxigenic C. difficile genome. Twenty-nine strains cultivated from stool specimens were evaluated by the Xpert systems as presumed C. difficile PCR ribotype 027 were confirmed as a C. difficile ribotype 176 based on ribotyping. A further 120 C. difficile strains of ribotype 176 were examined for the presence of genes tcdB, cdtB and deletion in position 117 in the tcdC gene. Our experience shows that due to the correspondence of the target places, C. difficile ribotype 176 may be interpreted as ribotype 027 by Xpert C. difficile Epi assay (Cepheid Inc., Sunnyvale, CA). Further molecular analysis as ribotyping based on capillary electrophoresis is needed to differentiate between C. difficile ribotypes 027 and 176 for appropriate epidemiological situation control on local and national levels.     

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 17. Can a mechanistic rationale be provided for non-genotoxic carcinogens identified in rodent bioassays?

In a recent survey of the results of the National Cancer Institute/National Toxicology Program's Carcinogenesis Bioassay Program, Ashby and Tennant (1988) drew attention to the high proportion of carcinogens that were non-genotoxic insofar as their response to the Salmonella-microsome test was concerned. The present review contrasts these findings with what is known mechanistically about non-genotoxic carcinogens that affect the tissues which are considered to be particularly prone to non-genotoxic tumor induction. Excessive and often thresholded increases in cellular proliferation in the affected tissues appear to be one common feature in tumor induction by these agents, which act either through cytotoxicity followed by regeneration or through hormone-mimetic action. It is suggested that a weight of the evidence approach on a chemical by chemical basis is necessary to decide the relevance of these agents to the human situation.     

6 or 9?

In this article the author offers an original interpretation of patterns found on the world's most ancient felts (Fifth Century BCE). These artifacts have been recovered from frozen burial mounds in the Altai Mountains. The interpretation presented here constitutes a new approach to the study of ornamentation as a system of symbols.     

Reply To-Healy D. and Waterhouse J.M.: the Circadian System and Affective Disorders: Clocks or Rhythms? Chronobiologic Disorders, Social Cues and the Light-Dark Cycle

In their monograph (1), Healy and Waterhouse quite thoughtfully distinguish between the altered shapes of circadian rhythms and their entrainment (synchronization). Although there is a great deal of evidence that various influences can alter the shape of circadian rhythms (“masking”), the literature on multiple time cues (zeitgebers) entraining different pacemakers is less convincing. In humans, evidence for nonphotic (social and activity-rest cycle) zeitgebers is restricted to human studies of anchor sleep (2), to data from Wever (3) and Czeisler (4) and to animal studies by Mrosovksy (5) and Turek (6). Until proven otherwise, it seems most likely that social cues primarily affect the sleep-wake cycle (activity-rest cycle), which- being loosely coupled to the endogenous circadian pacemaker-can be dissociated from it and the overt rhythms that are driven by it.     

F.G. syndrome: a rare and/or extremely polymorphic syndrome?

We report a case of mental retardation associated with multiple congenital anomalies suggesting an F.G. syndrome. We discuss problems concerning genetic counselling and the management of future pregnancies. Unfortunately, no concrete strategy, concerning prenatal diagnosis, can be proposed.     

A. A. Ukhtomskiĭ and I. P. Pavlov: a controversy or a dialogue?

Pavlov's concept of conditioned reflexes and Ukhtomskii theory of dominanta fall within the biological line in physiology. They unravel the integral adaptive and active nature of the organism behavior in the environment. It is impossible to develop modern concepts about the determinants of goal-directed behavior of animals and voluntary activity of humans without in-depth study of the achievements of these Russian physiological schools which not only formed the methodological basis for the current studies but also directed the way for their further development.     

Red leaves, insects and coevolution: a red herring?

W.D. (Bill) Hamilton proposed that coevolution between plants and herbivorous insects explains the bright autumnal colouration of leaves. Accordingly, plants invest in bright signals to reduce their herbivore load, whereas insects use these bright signals to identify less-defended hosts more efficiently. Archetti and Brown have recently revisited this theory by explaining its basic predictions and providing new research perspectives. Their work presents an important basis to our understanding of non-green leaf colouration, provided that alternative adaptive explanations on the photoprotective and antioxidant role of leaf pigments, or their possible function in crypsis to herbivores are incorporated into future research.