Effect of preinductin of metallothionein synthesis on clastogenicity of anticancer drugs in mice

Ippei Nakagaw; Emiko Nishi; Akira Naganuma; Nobumasa Imura

doi:10.1016/0165-7992(95)90019-5

Effect of preinductin of metallothionein synthesis on clastogenicity of anticancer drugs in mice

Ippei Nakagaw, Emiko Nishi, Akira Naganuma, Nobumasa Imura

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

The effect of pretreatment with metallothionein (MT) inducers (bismuth nitrate or zinc chloride) on clastogenicity of anticancer drugs was investigated. Bismuth nitrate (50 μmol/kg) or zinc chloride (400 μmol/kg) was administered s.c. to mice once a day for two days prior to treatment with 3.3 μmol/kg of cis-diamminedichloroplatinum(II) (cis-DDP), 3.4 μmol/kg of adriamycin (ADR), 72 μmol/kg of cyclophosphamide (CPA) or 0.41 μmol/kg of L-phenylalanine mustard (L-PAM). The frequency of occurrence of erythrocytes with micronuclei in bone marrow was increased by each anticancer drug at 24 h after treatment. Micronucleus formation was significantly prevented by pretreatment with either bismuth nitrate or zinc chloride. MT concentration in bone marrow cells of mice at the time of treatment with anticancer drugs increased to 2- and 3.5-fold by pretreatment with bismuth nitrate and zinc chloride, respectively. These results indicate that MT induction in bone marrow cells effectively prevents micronucleus induction of anticancer drugs.

Original language	English
Pages (from-to)	37-43
Number of pages	7
Journal	Mutation Research Letters
Volume	348
Issue number	1
DOIs	https://doi.org/10.1016/0165-7992(95)90019-5
Publication status	Published - 1995 Sep

Keywords

Adriamycin
Bismuth
Cyclophosphamide
L-Phenylalanine mustard
Metallothionein
Micronucleus test
Zinc
cis-DDP

ASJC Scopus subject areas

Medicine(all)

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title = "Effect of preinductin of metallothionein synthesis on clastogenicity of anticancer drugs in mice",

abstract = "The effect of pretreatment with metallothionein (MT) inducers (bismuth nitrate or zinc chloride) on clastogenicity of anticancer drugs was investigated. Bismuth nitrate (50 μmol/kg) or zinc chloride (400 μmol/kg) was administered s.c. to mice once a day for two days prior to treatment with 3.3 μmol/kg of cis-diamminedichloroplatinum(II) (cis-DDP), 3.4 μmol/kg of adriamycin (ADR), 72 μmol/kg of cyclophosphamide (CPA) or 0.41 μmol/kg of L-phenylalanine mustard (L-PAM). The frequency of occurrence of erythrocytes with micronuclei in bone marrow was increased by each anticancer drug at 24 h after treatment. Micronucleus formation was significantly prevented by pretreatment with either bismuth nitrate or zinc chloride. MT concentration in bone marrow cells of mice at the time of treatment with anticancer drugs increased to 2- and 3.5-fold by pretreatment with bismuth nitrate and zinc chloride, respectively. These results indicate that MT induction in bone marrow cells effectively prevents micronucleus induction of anticancer drugs.",

keywords = "Adriamycin, Bismuth, Cyclophosphamide, L-Phenylalanine mustard, Metallothionein, Micronucleus test, Zinc, cis-DDP",

author = "Ippei Nakagaw and Emiko Nishi and Akira Naganuma and Nobumasa Imura",

year = "1995",

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AU - Nakagaw, Ippei

AU - Nishi, Emiko

AU - Naganuma, Akira

AU - Imura, Nobumasa

PY - 1995/9

Y1 - 1995/9

N2 - The effect of pretreatment with metallothionein (MT) inducers (bismuth nitrate or zinc chloride) on clastogenicity of anticancer drugs was investigated. Bismuth nitrate (50 μmol/kg) or zinc chloride (400 μmol/kg) was administered s.c. to mice once a day for two days prior to treatment with 3.3 μmol/kg of cis-diamminedichloroplatinum(II) (cis-DDP), 3.4 μmol/kg of adriamycin (ADR), 72 μmol/kg of cyclophosphamide (CPA) or 0.41 μmol/kg of L-phenylalanine mustard (L-PAM). The frequency of occurrence of erythrocytes with micronuclei in bone marrow was increased by each anticancer drug at 24 h after treatment. Micronucleus formation was significantly prevented by pretreatment with either bismuth nitrate or zinc chloride. MT concentration in bone marrow cells of mice at the time of treatment with anticancer drugs increased to 2- and 3.5-fold by pretreatment with bismuth nitrate and zinc chloride, respectively. These results indicate that MT induction in bone marrow cells effectively prevents micronucleus induction of anticancer drugs.

AB - The effect of pretreatment with metallothionein (MT) inducers (bismuth nitrate or zinc chloride) on clastogenicity of anticancer drugs was investigated. Bismuth nitrate (50 μmol/kg) or zinc chloride (400 μmol/kg) was administered s.c. to mice once a day for two days prior to treatment with 3.3 μmol/kg of cis-diamminedichloroplatinum(II) (cis-DDP), 3.4 μmol/kg of adriamycin (ADR), 72 μmol/kg of cyclophosphamide (CPA) or 0.41 μmol/kg of L-phenylalanine mustard (L-PAM). The frequency of occurrence of erythrocytes with micronuclei in bone marrow was increased by each anticancer drug at 24 h after treatment. Micronucleus formation was significantly prevented by pretreatment with either bismuth nitrate or zinc chloride. MT concentration in bone marrow cells of mice at the time of treatment with anticancer drugs increased to 2- and 3.5-fold by pretreatment with bismuth nitrate and zinc chloride, respectively. These results indicate that MT induction in bone marrow cells effectively prevents micronucleus induction of anticancer drugs.

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KW - Micronucleus test

KW - Zinc

KW - cis-DDP

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