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

Nakagaw, Ippei; Nishi, Emiko; Naganuma, Akira; Imura, Nobumasa

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

Cited by 25 publications

(12 citation statements)

References 34 publications

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“…The best recovery of about 60% was obtained with 8 mg/kg ZnCl 2 used together with 50 mg/kg CP, but even with the highest (150 mg) CP dose, there was about 40% recovery of the bone marrow cells. In support of our results, the frequency of occurrence of erythrocytes with micronuclei in bone marrow of mice was increased by CP treatment, but micronucleus formation was significantly prevented by pretreatment with ZnCl 2 [24]. Similarly, 50 mg/kg CP increased more than five times the number of micronucleated erythrocytes in bone marrow of rat; however, with the treatment of 4 mg/kg zinc acetate, a high percent recovery was achieved [18].…”

Section: Discussionsupporting

confidence: 75%

Protective Effect of Zinc on Cyclophosphamide-Induced Hematoxicity and Urotoxicity

Ayhancı

Uyar

Aral

et al. 2008

Biol Trace Elem Res

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Cyclophosphamide (CP) is widely used for the treatment of neoplastic diseases; however, its toxicity causes dose-limiting side effects. Zinc (Zn) is an essential trace element and has important biological functions that control many cell processes including DNA synthesis, normal growth, reproduction, fetal development, bone formation, and wound healing. Therefore, the toxicity of CP and the possible protective effect of Zn on blood cells, bone marrow, and bladder of rat were investigated in this study. Intraperitoneal administration of 50, 100, or 150 mg/kg CP for 3 days caused, in a dose-dependent manner, reductions in the number of leukocytes, thrombocytes, and bone marrow nucleated cells and a serious urotoxicity. To explore whether CP-induced damages could be prevented by Zn, other groups of rats were pretreated with 4 or 8 mg/kg ZnCl 2 intraperitoneally for 3 days then challenged with respective doses of CP plus ZnCl 2 on day 4 for three more days. The results indicated that treatment of rats with Zn could dose-dependently alleviate CP-induced toxicities on blood cells, bone marrow cells, and urinary bladder. We suggest that Zn could be a potentially effective drug in the prevention of CP-related hematoxicity and urotoxicity.

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Section: Discussionsupporting

confidence: 75%

Protective Effect of Zinc on Cyclophosphamide-Induced Hematoxicity and Urotoxicity

Ayhancı

Uyar

Aral

et al. 2008

Biol Trace Elem Res

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“…Itoh and Shimada (1996) have reported that pretreatment with an MT inducer suppressed the MN induction by chromium compounds and selenium compounds. MN induced by anticancer drugs such as cisplatin, adriamycin, cyclophosphamide and Lphenylalanine mustard was also prevented by pretreatment with MT inducers (Nakagawa et al, 1995). These results suggest that MT may play a protective role against chromosomal aberration induced by several compounds including B [a]P.…”

Section: Discussionmentioning

confidence: 48%

“…In addition, MT can reduce the adverse effects of the chemotherapeutic agents adriamycin and cis-diamminedichloroplatinum (II) (cisplatin) and other alkylating agents. (Satoh et al, 1988;Naganuma et al, 1987;Nakagawa et al, 1995). Pretreatment with MT-inducing metals such as zinc and bismuth can suppress chemical carcinogenesis caused by 7,12-dimethylbenz [a]anthracene (DMBA), 3-methyl cholanthrene, cisplatin and melphalan (Poswillo and Cohen, 1971;Duncan and Dreosti, 1975;Satoh et al, 1993;Cherian et al, 1994).…”

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confidence: 99%

Protective role of metallothionein in benzo[a]pyrene-induced DNA damage

et al. 2009

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INTRODUCTION Benzo[a]pyrene (B[a]P) is one of the polycyclic aromatic hydrocarbons (PAH) referred to as a human carcinogen (IARC monographs, in preparation). B[a]P has beenshown to induce gene mutations, chromosomal aberrations and other types of genotoxic effects in in vitro and in vivo. Most humans are more or less constantly exposed to B[a]P. As a product of incomplete combustion, B[a]P is present in tobacco smoke, diesel engine exhaust, urban air, various types of processed foods, coal-tar, creosote, asphalt, and various occupational settings such as coal B[a]P is metabolized to 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) by cytochrome P450 (P450 or CYP). BPDE is the ultimate carcinogenic form of B[a]P and binds to the exocyclic nitrogen of deoxyguanosine in DNA. BPDE-DNA adducts in target tissues were closely related to development of cancer in animals and humans (Culp and Beland, 1994). In addition, oxidative DNA damage also plays an important role in the process of B[a]P carcinogenesis, because B[a]P produces quinone derivatives which easily generate reactive oxygen species (ROS) and oxidatively damage DNA (Penning et al., 1996). As a result of hydroxyl radical interaction with DNA, many types of oxidized a]P administration, although that of wild-type mice was only slightly changed. Because cytochrome P450 (CYP) plays a major role in the process of B[a]P metabolic activation, we attempted to reveal the effect of MT on metabolic activation of B[a]P. Although CYP1A activities were elevated in the livers of MT-I/II null mice and wild-type mice treated with B[a]P, it was not different between both strains of mice. In addition, a]P treatment, whereas MT was not detected in livers of MT-I/II null mice with or without B[a]P treatment. These results demonstrate that MT acts as an endogenous defensive factor against B[a]P-induced DNA damage.

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“…32) Anticancer drugs, such as cisplatin, adriamycin, cyclophosphamide and Lphenylalanine mustard, induced MN, but pretreatment with MT inducers could prevent this. 33) Recently, a few reports have described using MT-I/II null mice to demonstrate that the protective effects of Zn pretreatment on cisplatin-induced renal toxicity and X-irradiation-induced bone marrow injury were due to an induction of MT. 34,35) In the present study, Zn pretreatment suppressed the mutagenicity of B[a]P in wild-type mice but not in MT-I/II null mice.…”

Section: Discussionmentioning

confidence: 99%

Preventive Effect of Preinduction of Metallothionein on Mutagenicity Caused by Benzo[a]pyrene

Takaishi

Suzuki

Satoh

et al. 2010

JOURNAL OF HEALTH SCIENCE

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The effect of pretreatment with zinc (Zn) compounds on the mutagenicity of benzo [a]pyrene (B[a]P) was investigated using metallothionein (MT)-I/II null mice. MT-I/II null mice and wild-type mice were subcutaneously administered ZnSO 4 once a day for 2 days and gavaged B[a]P at 24 hr after the last injection of ZnSO 4 . B[a]Pinduced micronucleus frequencies were reduced by Zn pretreatment in the wild-type mice but not in the MT-I/II null mice. Zn administration significantly increased the concentration of MT in the liver and bone marrow cells of wild-type mice, but the statuses of other cellular antioxidants, such as glutathione, catalase and superoxide dismutase, were unchanged. In addition, the activity of a major B[a]P metabolic activation enzyme, cytochrome P450 1A, was unchanged by Zn treatment in both MT-I/II null mice and wild-type mice. These results suggest that Zn pretreatment protects against the mutagenicity of B[a]P through the induction of MT synthesis. The amount of MT produced in animals may determine their sensitivity to B[a]P exposure.

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

Cited by 25 publications

References 34 publications

Protective Effect of Zinc on Cyclophosphamide-Induced Hematoxicity and Urotoxicity

Protective Effect of Zinc on Cyclophosphamide-Induced Hematoxicity and Urotoxicity

Protective role of metallothionein in benzo[a]pyrene-induced DNA damage

Preventive Effect of Preinduction of Metallothionein on Mutagenicity Caused by Benzo[a]pyrene

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