Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.

Pretreatment of mice with low doses of methyl-CCNU was shown to reduce the toxicity of lethal doses of methyl-CCNU or melphalan administered one or two days following the low dose. There was an increase in survival rate, body weight, thymus and kidney wet weight. Tissue morphology was less affected...

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Main Authors:	Zimber, A., Perk, K., Livnat, I.
Format:	Online
Language:	English
Published:	Nature Publishing Group 1988
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246517/

id	pubmed-2246517
recordtype	oai_dc
spelling	pubmed-22465172009-09-10 Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma. Zimber, A. Perk, K. Livnat, I. Research Article Pretreatment of mice with low doses of methyl-CCNU was shown to reduce the toxicity of lethal doses of methyl-CCNU or melphalan administered one or two days following the low dose. There was an increase in survival rate, body weight, thymus and kidney wet weight. Tissue morphology was less affected in the primed mice as compared to mice receiving the high dose or a high-low dose combination. In mice implanted s.c. with Lewis lung carcinoma, priming with 5 mg kg-1 methyl-CCNU 2 days before injection of a very high (35 mg kg-1) dose significantly increased the lifespan as compared to treatment with the high dose alone or with high-low dose combination. When the dose of methyl-CCNU was further increased to 40 mg kg-1 toxic death occurred, which was, however, significantly reduced by 'priming' with the low dose given. When low-high dose combination was used twice (the high dose was given on day 7 or 9, and 18 or 20 after tumour inoculation), priming with 5 mg kg-1 (but not with 10 mg kg-1) two days prior to the high dose was beneficial in reducing toxic death (in two experiments) and either increasing lifespan or not significantly increasing it. In no case was there protection of the tumour by the low-high dose combinations. Nature Publishing Group 1988-03 /pmc/articles/PMC2246517/ /pubmed/3355764 Text en
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zimber, A. Perk, K. Livnat, I.
spellingShingle	Zimber, A. Perk, K. Livnat, I. Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.
author_facet	Zimber, A. Perk, K. Livnat, I.
author_sort	Zimber, A.
title	Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.
title_short	Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.
title_full	Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.
title_fullStr	Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.
title_full_unstemmed	Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.
title_sort	priming with low doses of methyl-ccnu reduce the toxicity of high doses of methyl-ccnu and melphalan, and increase the lifespan of mice implanted with lewis lung carcinoma.
description	Pretreatment of mice with low doses of methyl-CCNU was shown to reduce the toxicity of lethal doses of methyl-CCNU or melphalan administered one or two days following the low dose. There was an increase in survival rate, body weight, thymus and kidney wet weight. Tissue morphology was less affected in the primed mice as compared to mice receiving the high dose or a high-low dose combination. In mice implanted s.c. with Lewis lung carcinoma, priming with 5 mg kg-1 methyl-CCNU 2 days before injection of a very high (35 mg kg-1) dose significantly increased the lifespan as compared to treatment with the high dose alone or with high-low dose combination. When the dose of methyl-CCNU was further increased to 40 mg kg-1 toxic death occurred, which was, however, significantly reduced by 'priming' with the low dose given. When low-high dose combination was used twice (the high dose was given on day 7 or 9, and 18 or 20 after tumour inoculation), priming with 5 mg kg-1 (but not with 10 mg kg-1) two days prior to the high dose was beneficial in reducing toxic death (in two experiments) and either increasing lifespan or not significantly increasing it. In no case was there protection of the tumour by the low-high dose combinations.
publisher	Nature Publishing Group
publishDate	1988
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246517/
_version_	1611439559370866688

Priming with low doses of methyl-CCNU reduce the toxicity of high doses of methyl-CCNU and melphalan, and increase the lifespan of mice implanted with Lewis lung carcinoma.

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