Irradiated mice

MetaHoelement complexes may be useful for the post-irradiation treatment of radiation injury, based on the observation that several of these compounds accelerate recovery of, among other things, lympho/hemopoiesis. Preirradiation Mn2(0)(DIPS)g increases the survival of y-irradiated mice (103). Treatment of mice that have been exposed to an LD q q dose of y-rays plus Mn2(0)(DIPS)g either 1 or 3 h after irradiation also increases survival, which supports the hypothesis that this compound is an effective radiorecovery agent (105). Again, this increase in survival may result from the resynthesis of radiation-depleted Mn-dependent enzymes that facHitate the recovery of immunocompetence and tissue repair, as reported for Cu(II)2(DIPS)4. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

FIGURE 2 9-3 Intravenous administration of stem cells can reconstitute the blood forming system, and may provide cells to other tissues. In classical studies, Till and McCulloch administered dissociated bone marrow cells in the tail vein of lethally irradiated mice and found that the grafted cells repopulated the hematopoietic system and allowed the animals to survive. More recent studies suggest that blood cells also travel to sites of injury, where they may give rise to non-blood-tissue progeny. 

Urocanic acid (2-propanoic acid 3-[lH-imidazol-4-yl] is located superficially in the stratum comeum. Metabolism of epidermal UCA does not occur in situ due to the absence of urocanase, resulting in the accumulation of UCA in the epidermis. Upon UV exposure, naturally occurring trans-UCA converts to the d.s-isomer, in a dose dependent manner, until the photostationary state is reached, when equal quantities of trans- and m-UCA are found in the skin.15 Based on an analysis of the action spectrum for UV-induced immune suppression, and the fact that no immune suppression was observed in mice whose stratum comeum was previously removed by tape stripping, De Fabo and Noonan suggested that urocanic acid was the photoreceptor for UV-induced immune suppression.16 Since the initial experiments many others have documented, the ability of ris-UCA to initiate immune suppression, documented its presence in the serum of UV-irradiated mice, and demonstrated that m-UCA plays a role in UV-induced skin cancer induction. (For a more complete review of the role of m-UCA in immune suppression see two excellent reviews by Norval and colleagues.1718)... 

Kripke, M. L. et al., Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice, Proc. Natl. Acad. Sci. USA 89, 7516-7520, 1992. 

Pristane (2,6,10,14-tetramethylpentadecane) is a mineral oil known to induce arthritis, a disease also referred to as pristane-induced arthritis (PIA) [58], Susceptibility to PIA is MHC-haplotype dependent, in that DBA/1 (H2q) mice are susceptible whereas DBA/2 (H2d) are not, and is accompanied by a broad spectrum of autoantibodies, including anti-Rheuma Factor (RF), anti-collagen and antibodies to heat shock proteins (HSP). PIA is clearly immune dependent since nu/nu mice and irradiated mice do not develop PIA. PIA involves polyclonal T cell activation [59], particularly CD4+ cells [58], Intriguingly, mice can be protected from developing PIA by HSP65-specilic CD4+ Th2 cells [60],... 

Ornithine decarboxylase activity. Fixed oil (4.5%), Clupeidae brevortia tyrannus (4%), and Zea mays (1.5%) fixed oil (7.5%), Clupeidae brevortia tyrannus (1%), and Zea mays (1.5%) fixed oil (8.5%) and Zea mays (1.5%), administered orally to mice for 1 year, were active vs benzoyl peroxide-induced ornithine decarboxylase activity Oil, administered to 30 ultraviolet (UV)-irradiated Senear and SKH-1 mice at doses of 1/14% (A diet), 7.9/7.1% (B diet), and 15/0% (C diet) corn oil/coco-nut oil for 6 weeks, produced no increase in enzyme activity. The level of ornithine decarboxylase activity in the UV-irradiated mice fed diet A was significantly higher than in mice fed the B or C diet. In the SKH-1 mice, ornithine decarboxylase activity was increased by 3 weeks and was significantly higher in mice fed diet C than in mice fed diet A. There was no significant effect of dietary fat on UV-induced skin tumor incidence ". 

Fig. 3.1 Dose-incidence curves for different neoplasms in animals exposed to external radiation (A) myeloid leukemia in x-irradiated mice (°) (Upton et al., 1958) (B) mammary gland tumors at 12 months in gamma-irradiated rats (A) (Shellabarger et al., 1969) (C) thymic lymphoma in x-irradiated mice ( ) (Kaplan and Brown, 1952) (D) kidney tumors in x-irradiated rats (o) (Maldague, 1969) (E) skin tumors in alpha-irradiated rats (percentage incidence x 10) ( ) (Bums et al., 1968) (F) skin tumors in electron-irradiated rats (percentage incidence x 10) (A) (Bums et al., 1968) (G) reticulum cell sarcoma in x-irradiated mice (0) (Metalli et al., 1974) (H) lung adenomas in neutron-irradiated mice ( ) (Ullrich et al., 1976) (Modified from UNSCEAR, 1972) (from Upton, 1984).

Cole, L.J. and Nowell, P.C. (1964). Accelerated induction of hepatomas in fast neutron-irradiated mice injected with carbon tetrachloride, Ann. New Vbrk Acad. ScL 114,259. 

Hydrogen peroxide transformed mouse myeloid progenitor cells (FDC-Pl) from interleukin-3 dependence to factor independence, but only at cytotoxic concentrations (> 12/5 pmol/L). Such a transformation was not induced by non-specific insults to the cells, such as sodium fluoride or heat shock treatment. The transformed cells produced tumours when injected into pre-irradiated mice (Crawford Greenberger, 1991). Hydrogen peroxide (10 pmol/L) induced overexpression of the proto-oncogene c-jun in hamster tracheal epithelial (HTE) cells c-jun overexpression led to proliferation and increased growth rate, as well as increased anchorage-independence of HTE cells (Timblin et al., 1995). 

In cases where the cell line is a heterohybrid, that is, a human/mouse hybrid, it may be possible to grow the cell line as a tumor in sublethally irradiated mice and produce ascitic fluid... 

The native calcium-binding protease, calpain, which translocates to the cytosolic surface of membranes upon calcium binding, was enriched from a membrane preparation and shown to elicit high levels of protection (56-67%) in mice (Hota-Mitchell ef a/., 1997). This protein was first implicated in protective immunity as the target of a CD4+ T cell clone that could arm peritoneal macrophages to kill schistosomula in vitro (Jankovic ef a/., 1996). The same clone administered intraperitoneally, conferred 65% protection on irradiated mice challenged via this route with cercariae and recombinant IL-2 (this is a very artificial test from which results should be treated with caution). The large subunit of calpain was subse-... 

Restored antibody-forming capacity of irradiated mice by affecting lymphocytes 377... 

B23. Burlakova, E. B., and Dziuba, N. M., Synthetic inhibitors and natural antioxidants. II. The antioxidative activity of liver lipids of irradiated mice and die radioprotective effect of inhibitors of free radical reactions. Biofizika 11, 54—57 (1966). 

Two observations suggest near normal function for rcel cells. First, loss of Rcelp minimally impacts hematopoiesis in otherwise normal tissue [46]. Second, adoptive transfer of murine rcel fetal liver cells rescues hematopoiesis in lethally irradiated mice. Moreover, tissue-specific loss of Rcelp in liver also results in otherwise healthy mice, as judged histologically and biochemically (i.e., transaminase activity) [11]. These... 

Prabhakar KR, Veerapur VP, Parihar KV, Priyadarsini KI, Rao BSS, Unnikrishnan MK. (2006) Evaluation and optimization of radioprotective activity of Coronopus didymus Linn, in y-irradiated mice. Int JRadiat Biol 82 525-536. 

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