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Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates.

Publication ,  Journal Article
Spence, AM; Rasey, JS; Dwyer-Hansen, L; Grunbaum, Z; Livesey, J; Chin, L; Nelson, N; Stein, D; Krohn, KA; Ali-Osman, F
Published in: Radiother Oncol
June 1995

L-Homocysteine thiolactone (L-HCTL) was evaluated for its potential as an intravenously-administered central nervous system (CNS) radioprotector in C3H mice and F344 rats. Toxicity assessments in the mouse yielded a LD50 of 297 mg/kg and in the rat 389 mg/kg. Biodistribution studies in tumor-bearing mice showed that brain specimens contained more label at 10 min than the tumors but less at 30 or 60 min. Brain uptake relative to the tumors, the brain/tumor ratio, ranged between 0.5 and 3.3. The cervical spinal cord of non-tumor-bearing rats was irradiated with 32 Gy 137Cs with or without prior treatment with L-HCTL following which the time to forelimb or hindlimb paralysis was measured to determine the relative protective factors (RPFs) for this radiation dose. For forelimb paralysis the RPF was 1.9 (+/- 1.0, SD) and for hindlimb it was 2.0 (+/- 1.1, SD). 36B-10 glioma cells irradiated in vitro with or without L-HCTL and assayed for colony forming capacity demonstrated a dose modifying factor (DMF) of only 1.15 (+/- 0.16, SE). Rats bearing intracerebral 36B-10 glioma received 137Cs irradiation with or without L-HCTL after which the tumors were similarly assayed in vitro. From this the glioma DMF was 1.2 (+/- 0.30, SE). Compared to prior results with phosphorothioates our data show that the toxicity of L-HCTL is roughly the same as WR2721, WR77913 and WR3689 and that it distributes at higher levels in the CNS after systemic administration. L-HCTL may well equal these phosphorothioates at protecting normal CNS tissue without requiring administration directly into the cerebrospinal fluid-containing spaces and it does not protect the 36B-10 glioma.

Duke Scholars

Published In

Radiother Oncol

DOI

ISSN

0167-8140

Publication Date

June 1995

Volume

35

Issue

3

Start / End Page

216 / 226

Location

Ireland

Related Subject Headings

  • Tumor Cells, Cultured
  • Tissue Distribution
  • Spinal Cord
  • Rats, Inbred F344
  • Rats
  • Radiation-Protective Agents
  • Oncology & Carcinogenesis
  • Mice, Inbred C3H
  • Mice
  • Male
 

Citation

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Spence, A. M., Rasey, J. S., Dwyer-Hansen, L., Grunbaum, Z., Livesey, J., Chin, L., … Ali-Osman, F. (1995). Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates. Radiother Oncol, 35(3), 216–226. https://doi.org/10.1016/0167-8140(95)01543-p
Spence, A. M., J. S. Rasey, L. Dwyer-Hansen, Z. Grunbaum, J. Livesey, L. Chin, N. Nelson, D. Stein, K. A. Krohn, and F. Ali-Osman. “Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates.Radiother Oncol 35, no. 3 (June 1995): 216–26. https://doi.org/10.1016/0167-8140(95)01543-p.
Spence, A. M., et al. “Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates.Radiother Oncol, vol. 35, no. 3, June 1995, pp. 216–26. Pubmed, doi:10.1016/0167-8140(95)01543-p.
Spence AM, Rasey JS, Dwyer-Hansen L, Grunbaum Z, Livesey J, Chin L, Nelson N, Stein D, Krohn KA, Ali-Osman F. Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates. Radiother Oncol. 1995 Jun;35(3):216–226.
Journal cover image

Published In

Radiother Oncol

DOI

ISSN

0167-8140

Publication Date

June 1995

Volume

35

Issue

3

Start / End Page

216 / 226

Location

Ireland

Related Subject Headings

  • Tumor Cells, Cultured
  • Tissue Distribution
  • Spinal Cord
  • Rats, Inbred F344
  • Rats
  • Radiation-Protective Agents
  • Oncology & Carcinogenesis
  • Mice, Inbred C3H
  • Mice
  • Male