Protection against late effects of radiation by S-2-(3-aminopropylamino)-ethylphosphorothioic acid.

نویسندگان

  • D J Grdina
  • B A Carnes
  • D Grahn
  • C P Sigdestad
چکیده

We have demonstrated that S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR2721) administered to mice 30 min prior to a relatively low dose of ionizing radiation is effective in protecting against radiation-induced carcinogenesis and subsequent life shortening. Female C57BL/6JANL x BALB/cJANL F1 mice, 200 per group, were exposed to gamma radiation at a dose of 206 cGy. Additional groups of 200 animals were sham treated, given injections of 400 mg/kg of WR2721, or administered WR2721 and the irradiated with 60Co photons at doses of 206 cGy or 417 cGy. Mice were treated at 110 days of age. They were housed five to a cage and were checked daily throughout life. All deceased animals were necropsied, and tissues were removed and fixed for histopathological analysis. Over 90% of the animal deaths were due to tumor involvement. WR2721 afforded significant protection (P = 0.0016) against radiation-induced malignancies (i.e., a total of 164 tumor codes were used) following a dose of 206 cGy. Protection against lymphoreticular tumors in particular was significant (P = 0.0165). Subsequent survival time in WR2721-protected animals (compared with matched irradiated controls) was extended by 65 days. Mice irradiated with 417 cGy following administration of WR2721 exhibited a response similar to those irradiated without the protector at a dose of 206 cGy (P = 0.26). Cumulative survival curves for unirradiated mice were unaffected by a single dose of WR2721. These data indicate a potential novel benefit for radioprotectors in cancer therapy. WR2721 and similar aminothiols may be effective adjuvants for reducing the risk of therapy-induced secondary cancers in patients who have an excellent prognosis for cure and long-term survival.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid.

Through an in vivo and in vitro analysis of the absorption kinetics of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) in the normal tissues and solid tumors of mice, rats, and rabbits, it has been demonstrated that normal tissues actively concentrate WR-2721 against a concentration gradient, whereas solid tumors passively absorb it, or, if active concentration of WR-2721 is present...

متن کامل

Protective effects of S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation damage of normal tissues and a fibrosarcoma in mice.

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was investigated for its protective effect against radiation-produced damage of jejunum, testis, lung, hair follicles, and a fibrosarcoma of C3Hf/Kam mice. Most of these tissues were radioprotected, and the degree of radioprotection depended on the dose of WR-2721 and the time interval between administration of WR-2721 and radiation tr...

متن کامل

Protection against Late Effects of Radiation by ,S-2-(3-Aminopropylamino)- ethylphosphorothioic Acid1

We have demonstrated that S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR2721) administered to mice 30 min prior to a relatively low dose of ionizing radiation is effective in protecting against radiation-induced carcinogenesis and subsequent life shortening. Female C57BL/6JANL x BALB/cJANL F, mice, 200 per group, were exposed to gamma radiation at a dose of 206 cGy. Additional groups of ...

متن کامل

Inhibition of radiation carcinogenesis in mice by S-2-(3-aminopropylamino)-ethylphosphorothioic acid.

We have demonstrated that S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) given to mice prior to ionizing radiation inhibits development of radiation-induced sarcomas. The right hind legs of C3Hf/Kam mice were exposed to single doses of gamma-rays ranging from 3400 to 5700 rads. Thirty min before irradiation, approximately one-half of the mice were given i.p. injections of WR-2721 (...

متن کامل

Protection by S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation-induced leg contractures in mice.

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was shown to provide marked protection against development of radiation-induced leg contractures in C3Hf/Kam mice whose legs were exposed to single doses of gamma-radiation. The radiation doses ranged from 3300 to 6200 rads delivered to the right hind thighs from two parallelly opposed 137Cs sources. WR-2721 was given i.p. 30 min befor...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cancer research

دوره 51 16  شماره 

صفحات  -

تاریخ انتشار 1991