Immunological response of the rat to infection with Taenia taeniaeformis: protective antibody response to implanted parasites.

Intraperitoneally implanted metacestodes of either T. taeniaeformis or T. crassiceps in rats provoked a high degree of resistance to oral challenge with eggs of T. taeniaeformis. This resistance was passively transferred to normal recipients with serum. Immunoglobulin fractions of immune serum containing IgG₁ or IgM were most effective in passive transfer and little activity was associated with IgG₂ antibodies. No skin-sensitizing antibodies were detectable in immune sera. These findings are in sharp contrast to previous observations involving protective immunoglobulins and reaginic antibodies in serum from rats with hepatic cysticerci of T. taeniaeformis. Possible reasons for this are discussed. Cysticerci implanted into normal rats survived for at least 21 days with no sign of host rejection, whereas those implanted into rats with hepatic infections with T. taeniaeformis were killed and encapsulated. Similar results were obtained by implanting cysticerci in normal rats given inoculations of complete Freund's adjuvant. Repeated inoculations of immune serum had no effect on the survival of implanted cysticerci, and it was concluded that exposure to infection by oncospheres provokes cellular defense mechanisms which can be effective against cysticerci in abnormal sites. Why these mechanisms are inoperative against hepatic cysticerci remains unclear.     

Epidemiological Assessment of Hormesis in Studies with Low-Level Exposure

Despite its resurgence within toxicology and, specifically, risk assessment, the concept of hormesis remains peripheral to current epidemiological practice. In this paper we examine some reasons for this, focusing on applications within occupational and environmental epidemiology. Unclear in the existing literature is whether hormesis pertains to a single biological mechanism or response, or the aggregate effect of all correlates of exposure. Although J-shaped and U-shaped relationships between risk factors and disease endpoints have been identified epidemiologically, it is unclear whether such patterns reflect biological hormesis or a combination of factors resulting in a hormetic-looking relationship. Given the potential importance of assessing hormetic responses in epidemiological studies, we identify and discuss key limitations of epidemiology in validly detecting and interpreting hormesis. For example, most observational occupational and environmental studies lack the ability to determine the dose received by each individual, and therefore poor surrogates of exposure are frequently used, potentially introducing considerable systematic and random error. Further, because exposure is not randomly assigned to humans, the potential for confounding is great. Finally, using a simple simulation to assess the impact of ignoring hormesis in the analysis of epidemiological data containing mild hormesis, we demonstrate a resulting “hormetic bias,” in which relative risks at exposure levels above the hormetic region are systematically overestimated.     

植物对增强UV-B辐射的防御机制研究进展

由于大气同温层的臭氧层逐渐被破坏变薄,增加了太阳UV-B辐射抵达地球表面的强度,对植物产生不同程度的影响.本文综述了近年来有关植物对增强UV-B辐射的防御机制,包括植物在生长、繁育与次生代谢过程中存在的防御机制、植物体内生物大分子对于UV-B辐射增强的防御和不同植物对于UV-B辐射增强的防御能力的差异,以及如何有效地利用该机制;同时提出了今后研究的方向和重点.     

Radiation Hormesis and Cancer

Despite the long history of radiation hormesis and the public health concerns with low-level exposures to ionizing radiation, there has been surprisingly little formal evaluation of whether hormetic effects are displayed with respect to radiation exposure and cancer incidence (i.e., reduced cancer risk at low radiation doses compared to controls, enhanced cancer risk at higher doses) until relatively recently. This paper reviews data relevant to the question of radiation hormesis and cancer with particular emphasis on experimental studies in animal models exposed to low levels of ionizing radiation. Data exist that provide evidence both consistent with and/or supportive of radiation hormesis. Other biomedical research provides potentially important mechanistic insight: low dose exposures have the capacity to activate immune function to prevent the occurrence of tumor development and metastasis; low doses of radiation have been shown to reduce mutagenic responses and induce endogenous antioxidant responses. These findings are consistent with epidemiological data suggesting an inverse relationship between background radiation and cancer incidence and with occupational epidemiological investigations in which low-dose exposure groups display markedly lower standardized mortality rates than the referent or control group.     

Ascorbate/iron mediation of hydroxyl free radical damage to PBR322 plasmid DNA

Plasmid PBR322 DNA has been exposed to hydroxyl free radicals generated from an ascorbate/Fe system. Hydroxyl free radical scavengers as well as the iron chelator desferroxamine and catalase inhibit the DNA nicking which occurs, but superoxide dismutase had no effect. The DNA nicking was temperature dependent, occuring more rapidly at higher temperatures. The rate of DNA nicking was accelerated by the addition of hydrogen peroxide. There was an early lag phase in DNA nicking, even though the rate of hydroxyl free radical generation, as assessed by salicylate hydroxylation, showed no lag phase. It is considered that the early hydroxyl free radical damage to DNA may be biologically very important in mutagenic and carcinogenic processes.     

Cytotoxicity, cellular uptake and DNA damage by daunorubicin and its new analogues with modified daunosamine moiety

Daunorubicin (DRB) and its two analogues containing a trisubstituted amidino group at the C-3′ position of the daunosamine moiety have been compared regarding their cytotoxic activity, cellular uptake, subcellular localization and DNA damaging properties. An analogue containing in the amidino group a morpholine moiety (DRBM) as well as an analogue with a hexamethyleneimine moiety (DRBH), tested against cultured L1210 cells, exhibited lower cytotoxicity then DRB. The decrease of cytotoxic activity was not related to cellular uptake and subcellular localization of drugs. Although all tested drugs were active in the induction of DNA breaks and DNA–protein crosslinks, they differed in the mechanism of induction of DNA lesions. DRB produced DNA breaks mediated solely by topoisomerase II, whereas DRBM and DRBH induced two types of DNA breaks by two separate processes. The first is related to the inhibition of topoisomerase II and the second presumably reflects a covalent binding of drug metabolites to DNA. It is hypothesized that the replacement of the primary amino group (–NH₂) at the C-3′ position of the daunosamine moiety by a trisubstituted amidino group (–N=CH–NRR) may be a route to the synthesis of anthracycline derivatives with enhanced ability to form covalent adducts to DNA.     

Structural basis for recruitment of the CHK1 DNA damage kinase by the CLASPIN scaffold protein

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Ionizing radiation‐induced long‐term expression of senescence markers in mice is independent of p53 and immune status

Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR‐induced senescence markers could persist long‐term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16^INK4a expression, two hallmarks of cellular senescence and aging. BrdU‐labeling experiments revealed that IR‐induced damaged cells are preferentially eliminated, at least partially, in a tissue‐dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild‐type and Rag2^?/? γC^?/? mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long‐term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.     

紫外线-B辐射对植物DNA及蛋白质的影响

大气平流层中的臭氧衰减,导致太阳辐射中的紫外辐射量有明显的增加,其中UV-B辐射对植物会产生不同程度的影响。分子生态学理论认为,UV-B辐射对植物造成的损伤,首先伤害植物的生物大分子,即进行光化学修饰。本文就臭氧衰减对生态环境和植物的影响途径进行了讨论,重点论述了UV-B辐射对植物蛋白质合成的抑制和DNA的损伤修复途径。并应用分子生物学技术研究植物对UV-B辐射的抗性机理和DNA修复技术的前景进行了展望。     

No evidence for radiation-induced clastogenic factors after in vitro or in vivo exposure of human blood

Experiments were performed with human plasma irradiated in vitro or in vivo in order to evaluate the extent to which clastogenic factors might disturb the adaptive response to DNA-damaging factors currently studied in our laboratory. The studies were carried out with plasma isolated from whole blood given 4 Gy of X-rays in vitro and with plasma from people receiving local radiotherapy at a total dose of about 60 Gy gamma rays. Addition of irradiated plasma to culture medium did not result in a statistically significant increase in structural aberrations in chromosomes of non-irradiated normal blood.     

辐射相关microRNA研究进展

microRNA(miRNA)是一类由内源基因编码的长度约22核苷酸的非编码单链RNA分子,主要以碱基互补方式与靶基因mRNA的3'非翻译区特异性结合,通过降解mRNA或抑制蛋白翻译合成而实现对靶基因的转录后调控。研究发现,miRNA在电离辐射诱导的生物学反应中发挥重要作用。我们从以下层面概述辐射相关miRNA的研究进展,即辐射调节miRNA表达、miRNA对辐射后DNA损伤的调节、miRNA参与的辐射生物学效应。