Prophylactic effects of amine oxides in radiation injury in mice

ABSTRACT IN 1957, Haley _et al._ 1 found that quinoxaline-1,4-di-N-oxide reduced X-radiation mortality in mice by 50 per cent. Two mechanisms were involved, reduction of bacteræmia1 and

interaction with X-ray-produced oxidizing radicals2. Comparisons have been made of other N-oxides (Table 1) using groups of 20 _CF_-1 mice and the same radiation conditions as before1. The

250 mgm./kgm. oral dose of drugs was given 24 hr. prior to irradiation with 550 r. The two quinoxaline derivatives significantly increased the _ST_ 50 day but had less effect on total

survival than quinoxaline-1,4-di-N-oxide. Erythromycin N-oxide significantly reduced the _ST_ 50 day and total survival while its anhydro derivative was equivalent to

quinoxaline-1,4-di-N-oxide as a radiation prophylactic. All the above compounds are readily absorbed, excreted slowly in the urine and exert antibiotic effects so the radiation bacteræmia

could be reduced. On the other hand not all of them can interact with equal facility with the radiation-produced oxidizing radicals. Examination of the chemical structures involved indicated

that an amine oxide either in an unsaturated ring, for example, quinoxaline or within one carbon atom of a double bond, for example, anhydroerythromycin is necessary if oxidizing radicals

are to be prevented from exerting their deleterious effects. In the dimethyl-substituted quinoxaline compounds difficulties in oxidizing the methyl groups are probably the reason for the

decrease in protectant activity even though Francis _et al._ 4 showed that hydroxylation in the 2 position occurs _in vivo_. With erythromycin N-oxide, the double bond is lacking and the

compound can be oxidized only with difficulty even _in vitro_ 5. Thus, it would appear that amine oxides with the above chemical structures can reduce mortality from ionizing radiation when

administered orally 24 hr. prior to exposure. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access

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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS A DERIVATIVE OF VITAMIN B3 APPLIED SEVERAL DAYS AFTER EXPOSURE REDUCES LETHALITY OF SEVERELY

IRRADIATED MICE Article Open access 12 April 2021 INVESTIGATING THE IMPACT OF LONG TERM EXPOSURE TO CHEMICAL AGENTS ON THE CHROMOSOMAL RADIOSENSITIVITY USING HUMAN LYMPHOBLASTOID GM1899A

CELLS Article Open access 16 June 2021 TOTAL BODY IRRADIATION CAUSES A CHRONIC DECREASE IN ANTIOXIDANT LEVELS Article Open access 24 March 2021 REFERENCES * Haley, T. J., Flesher, A. M.,

Veomett, R., and Vincent, J., _Proc. Soc. Exp. Biol. Med._, _N.Y._, 96, 579 (1957). Article  CAS  Google Scholar  * Haley, T. J., Abstr. of Papers, Amer. Chem. Soc., 134th Meeting, Sept.

7–12, 1958, 19-0. * Litchfield, jun., J. T., _J. Pharmacol._, 97, 399 (1949). Google Scholar  * Francis, J., Landquist, J. K., Levi, A. A., Silk, J. A., and Thorp, J. M., _Biochem. J._, 63,

455 (1956). Article  CAS  Google Scholar  * Flynn, E. H., Sigal, jun., M. V., Wiley, P. F., and Gerzon, K., _J. Amer. Chem. Soc._, 76, 3121 (1954). Article  CAS  Google Scholar  Download

references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department and Laboratories of Nuclear Medicine and Radiation Biology, School of Medicine, University of California, Los Angeles

THOMAS J. HALEY, ANNA M. FLESHER & NATHAN KOMESU Authors * THOMAS J. HALEY View author publications You can also search for this author inPubMed Google Scholar * ANNA M. FLESHER View

author publications You can also search for this author inPubMed Google Scholar * NATHAN KOMESU View author publications You can also search for this author inPubMed Google Scholar RIGHTS

AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE HALEY, T., FLESHER, A. & KOMESU, N. Prophylactic Effects of Amine Oxides in Radiation Injury in Mice.

_Nature_ 184, 198 (1959). https://doi.org/10.1038/184198a0 Download citation * Issue Date: 18 July 1959 * DOI: https://doi.org/10.1038/184198a0 SHARE THIS ARTICLE Anyone you share the

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