[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]
Re: New paper on beneficial effects of WBI in mice
From: "Jacobus, John (OD/ORS)" <jacobusj@ors.od.nih.gov>
> Jim,
> Since you asked for comments and Philippe was kind enough to supple a copy
> of the abstract, I will take up your request.
>
> Forgive me for having a skeptical eye, but the possible effect would be a
> response of the immune system to cell damage for the 0.5 Gy (50 rad)
> exposure. Again, whether this is a good or bad response is going to be
> based on several factors and what is the eventual outcome is to the animal.
> Did the mice live longer? Did they develop any malignancies? I would be
> interested to see a fractionation of the dose over different intervals to
> see how the levels of glutathione changed.
>
> I really know little of the functioning of glutathione in normal and
> diseases animals. Obviously it is exists at some normal level in the body.
> What function dose is normally play? Does it destroy damaged cells in the
> body, or only foreign pathogens? What is the mechanism that causes levels
> to change?
>
> As always, a interesting abstract.
>
> Have a good weekend.
>
> -- John
John,
The papers I previously provided explained this role, especially in
reducing cancer (NK activity effects both cancer and infection); and this
paper provides some brief explanation and a few of the relevant refs on
health effects. I can send the full paper if you want to review it (I'm at
AAAS meeting again tomorrow and Monday), but the following refs/background
from the paper responds to your questions:
(I have many of these papers, and most abstracts are on PubMed.)
Some of the relevant refs are:
7. James, S. J., and T. Makinodan. T cell potentiation in normal
autoimmune-prone mice after extended exposure to small doses of ionizing
radiation and/or caloric restriction: Int. J. Radiat. Biol. 53 137152. 1988
12. Nogami, M., J. T. Huang, S. J. James, J. M. Lubinski, and T. Makinodan.
Mice chronically exposed to low dose ionizing radiation possess splenocytes
with enhanced proliferation capacity and elevated levels of HSP-70 mRNA and
protein: Int. J. Radiat. Res. 63 775786. 1993
13. Nogami, M., J. T. Huang, L. T. Nakamura, and T. Makinodan. T cells are
the cellular target of the proliferation-augmentating effect of chronic
low-dose ionizing radiation in mice: Radiat. Res. 139 4752. 1994
14. Liu, S. Z., Z. B. Hann, and W. H. Liu. Changes in lymphocyte reactivity
to modulatory factors following low dose ionizing radiation: Biomed.
Environ. Sci. 7 130135. 1994
16. Chen, S. L., L. Cai, Q. Y. Meng, S. Xu, H. Wan, and S. Z. Liu. Low-dose
whole body irradiation (LD-WBI) changes protein expression of mouse
thymocytes: Effect of a LD-WBI-enhanced protein RIP10 on cell proliferation
and spontaneous or radiation-induced thymocytes apoptosis: Toxicol. Sci. 55
97106. 2000
17. Ibuki, Y., and R. Goto. Enhancement of concanavalin A-induced
proliferation of spleno-lymphocytes by small-dose-irradiated macrophages: J.
Radiat. Res. 35 8391. 1994
21. Pieri, C., M. Moroni, and R. Recchioni. Glutathione influences the
proliferation as well as the extent of mitochondrial activation in rat
splenocytes: Cell Immunol. 145 210217. 1992,
28. Meister, A. Glutathione deficiency produced by inhibition of its
synthesis, and its reversal; application in research and therapy: Pharmacol.
Ther. 51 155194. 1991,
29. Kojima, S., O. Matsuki, T. Nomura, A. Kubodera, Y. Honda, S. Honda, H.
Tanooka, H. Wakasugi, and K. Yamaoka. Induction of mRNAs for
glutathione-related proteins in mouse liver by small doses of gamma-rays:
Biochim. Biophys. Acta. 1381 312318. 1998,
30. Kojima, S., O. Matsuki, T. Nomura, N. Shimura, A. Kubodera, K. Yamaoka,
H. Tanooka, H. Wakasugi, Y. Honda, and T. Sasaki. Localization of
glutathione and induction of glutathione synthesis-related proteins in mouse
brain by small doses of gamma-rays: Brain Res. 808 262269. 1998,
31. Kojima, S., K. Teshima, and K. Yamaoka. Mechanisms involved in the
elevation of glutathione in RAW 264. 7 cells exposed to low doses of
gamma-rays: Anticancer Res. 20 15891594. 2000,
32. Teshima, K., A. Yamamoto, K. Yamaoka, and S. Kojima. Involvement of
calcium ion in elevation of mRNA for gamma-glutamyl cysteine synthetase
(-GCS) induced by low-dose gamma-rays: Int. J. Radiat. Biol. 76 16311639.
2000,
33. Kojima, S., S. Matsumori, H. Ishida, and K. Yamaoka. Possible role of
elevation of glutathione in the acquisition of enhanced proliferation of
mouse splenocytes exposed to small-dose gamma-rays: Int. J. Radiat. Biol. 76
16411647. 2000,
36. Hiraishi, H., A. Terano, S. Ota, H. Mutoh, T. Sugimoto, T. Harada, M.
Razandi, and K. J. Ivey. Protection of cultured rat gastric cells against
oxidant-induced damage by exogenous glutathione: Gastroenterology. 106
11991207. 1994,
37. Luckey, T. D. Radiation hormesis in cancer mortality: Int. J. Occup.
Med. Toxicol. 3 173193. 1994,
38. Luckey, T. D. Radiation Hormesis: CRC Press, Boca Raton, FL, 1991.
39. Safwat, A. The immunobiology of low-dose total-body irradiation: More
questions than answers: Radiat. Res. 153 599604. 2000, [ABSTRACT]
40. Anderson, R. E., S. Tokuda, W. L. Williams, and N. L. Warner.
Radiation-induced augmentation of the response of A/J mice to SaI tumor
cells: Am. J. Pathol. 108 2438. 1982,
41. Sakamoto, K., M. Miyamoto, and N. Watabe. The effect of small-dose total
body irradiation on tumor control: Jpn. J. Cancer Chemother. 14 15451549.
1987,
42. Hosoi, Y., and K. Sakamoto. Suppressive effect of small dose total body
irradiation on lung metastasis: Dose dependency and effective period:
Radiother. Oncol. 26 177179. 1993,
43. Prussia, B. Lymphokine activated killer cells. Natural killer cells and
cytokines: Curr. Opin. Immunol. 3 4955. 1991,
44. Furukawa, T., S. N. Meydani, and J. B. Blumberg. The potential benefits
of dietary glutathione on immune function and other practical implications:
In Glutathione: Metabolism and Physiological Functions (J. Vina, Ed.), pp.
351366. CRC Press, Boca Raton, FL, 1990.
48. Nguyen, Q. H., R. L. Roberts, B. J. Ank, S. L. Lin, C. K. Lau, and E. R.
Stiehm. Enhancement of antibody-dependent cellular cytotoxicity of neonatal
cells by interleukin-2 (IL-2) and IL-12: Clin. Diagn. Lab. Immunol. 5
98104. 1998
49. Vicker, M. G., H. Bultmann, U. Glade, and T. Hafker. Ionizing radiation
at small dose induces inflammatory reaction in human blood: Radiat. Res. 128
251257. 1991
50. Ishii, K., Y. Hosoi, T. Ono, and K. Sakamoto. Enhanced proliferation and
IL-1 production of mouse splenocytes by small dose whole body X-irradiation:
Physiol. Chem. Phys. Med. NMR. 28 714. 1996
And from the paper:
"INTRODUCTION
"Low doses of ionizing radiation induce various effects, including
radioadaptive responses (14) , activation of immune function (58) ,
stimulation of the growth rate (9) , and enhancement of resistance to
high-dose radiation (10, 11) . These phenomena have sometimes been called
radiation hormesis. Little is known about the mechanisms involved. Nogami et
al. demonstrated an elevated proliferative activity in response to mitogenic
stimulation in splenocytes of mice exposed to low-dose whole-body radiation
and showed that the cells involved were T cells. Low-dose irradiation also
elevated the constitutive levels of heat-shock protein 70 (Hsp70, now known
as Hspa4) mRNA and Hsp72 (now known as Hspa1b) in the cells. They further
showed that the cells from irradiated mice responded to T-cell
receptor-specific anti-CD3 stimulation by producing more Hspa4 mRNA and
Hspa1b and by proliferating more extensively than T cells from
sham-irradiated mice (12, 13) . Liu et al. reported that low-dose whole-body
irradiation increased the proliferative reactivity of splenic and thymic
lymphocytes to suboptimal concentrations of various mitogens in mice, and
that the immune enhancement was associated with an increased splenic
catecholamine content and a lowering of the serum corticosterone level (14,
15) . They showed that low-dose irradiation could stimulate these effects
through facilitation of signal transduction in lymphocytes. More recently,
the same group isolated a 10-kDa protein (Rip10) which was induced in the
cytoplasm of thymocytes after low-dose whole-body irradiation, and they
suggested a role for this protein in modulating the proliferation of
thymocytes and splenocytes (16) . Ibuki and Goto reported that low-dose
whole-body irradiation enhanced the concanavalin A (Con A)-induced
proliferation of splenocytes only when splenic macrophages were
simultaneously stimulated by the radiation (17) .
"It has been well documented that immune function is linked to the
release of reactive oxygen species (ROS). An excess amount of ROS is
commonly eliminated by endogenous antioxidant systems, thereby preventing
injury to DNA, intracellular proteins and membrane lipids. Thus
immunocompetent cells contain compounds which act to maintain the
antioxidant/oxidant (redox) balance. Reduced glutathione (GSH) has direct or
indirect roles in many biological processes, including protein and DNA
synthesis, amino acid transport, activation of enzyme activities, activation
of metabolism, and protection of cells from damage caused by ROS (18) .
Depletion of GSH can lead to increased lipid peroxidation with concomitant
changes in membrane permeability and cell damage, while an increase in the
level of this antioxidant enhances antioxidant protection and cell function.
Optimal immune function requires proper levels of GSH, and exogenous
provision of thiol-group donors is beneficial for immunocompetent cells
(1923) . Most cell damage caused by ionizing radiation is mediated by ROS
generated from the interactions of radiation and water molecules in cells
(2426). Intracellular GSH scavenges these ROS and protects some cells from
radiation toxicity (27, 28) . In our previous studies, we examined the
changes in the levels of endogenous GSH in mice exposed to whole-body gamma
radiation and found that low doses of radiation increased GSH levels
significantly in organs such as the liver, pancreas and brain (2932) . More
recently, it has been shown that the induction of endogenous GSH after
irradiation is responsible for the enhancement of Con A-induced
proliferation of mouse splenocytes (33).
"In this study, we examined whether the increase in the level of
glutathione induced by low doses of rays is involved in the appearance of
enhanced NK activity in mouse splenocytes."
This explains why cancer and infections can be reduced by LDR. The
triggering mechanisms are becoming better known. We don't need to know them
to know the effect - metallurgists still don't know fundamental
atomic/molecular bases for metal annealing and fatigue, but we can build
pressure vessels that don't explode any more :-)
Regards, Jim
===========
> John Jacobus, MS
> Certified Health Physicist
> 3050 Traymore Lane
> Bowie, MD 20715-2024
>
> E-mail: jenday1@email.msn.com (H)
>
> -----Original Message-----
> From: Philippe Duport [mailto:pduport@uottawa.ca]
> Sent: Thursday, February 14, 2002 2:39 PM
> To: Field, R. William; Muckerheide; rad-sci-l@ans.ep.wisc.edu;
> radsafe@list.vanderbilt.edu
> Subject: Re: New paper on beneficial effects of WBI in mice
>
>
>
>
> Here is the Medline abstract:
>
> 1: Radiat Res 2002 Mar;157(3):275-280
>
>
> Elevation of Glutathione Induced by Low-Dose Gamma Rays and its Involvement
> in Increased Natural Killer Activity.
>
> Kojima S, Ishida H, Takahashi M, Yamaoka K.
>
> Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi,
> Chiba 278-0022, Japan;; Author to whom correspondence should be addressed at
> Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi,
> Chiba 278-0022, Japan; kjma@rs.noda.sut.ac.jp
>
> Kojima, S., Ishida, H., Takahashi, M. and Yamaoka, K. Elevation of
> Glutathione Induced by Low-Dose Gamma Rays and its Involvement in Increased
> Natural Killer Activity. Radiat. Res. 157, 275[?]--[?]280 (2002).We examined
> the relationship between the induction of an increase in the level of
> glutathione and the elevation of natural killer (NK) activity in mouse
> splenocytes by a low dose of [gamma] rays. The glutathione levels in mouse
> splenocytes increased significantly between 2 h and 6 h after whole-body
> [gamma] irradiation at 0.5 Gy, peaked at 4 h, and then decreased almost to
> the level before irradiation by 12 h postirradiation. A significant
> enhancement of NK activity was found in the splenocytes obtained from
> whole-body-irradiated mice between 4 and 6 h postirradiation. Reduced
> glutathione (GSH) added exogenously to splenocytes obtained from normal mice
> enhanced both the total cellular glutathione content and the NK activity in
> a dose-dependent manner. Other precursors of de novo GSH synthesis, such as
> cysteine, N-acetylcysteine and oxidized glutathione, also increased the
> activity. These enhancements were completely blocked by buthionine
> sulfoximine, an inhibitor of de novo GSH synthesis. We conclude that the
> induction of endogenous glutathione in living cells immediately after
> low-dose [gamma] irradiation is at least partially responsible for the
> appearance of enhanced NK activity.
>
> PMID: 11839089 [PubMed - as supplied by publisher]
>
> _____
>
>
> . . .
>
> Your comments are most welcome.
>
> Regards, Jim Muckerheide
>
>
>
************************************************************************
You are currently subscribed to the Radsafe mailing list. To unsubscribe,
send an e-mail to Majordomo@list.vanderbilt.edu Put the text "unsubscribe
radsafe" (no quote marks) in the body of the e-mail, with no subject line. You can view the Radsafe archives at http://www.vanderbilt.edu/radsafe/