7,12-DMBA-induced rat leukemia: a review with insights into future research

Sugiyama, Taketoshi; Osaka, Mariko; Koami, Kenichi; Maeda, Sakan; Ueda, Norifumi

doi:10.1016/s0145-2126(02)00045-0

Cited by 34 publications

(24 citation statements)

References 86 publications

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“…We have previously reported (Ito et al, 1982;Sugiyama et al, 2002) that the administration of Sudan III, an inducer of drug-metabolizing enzymes, 24 h before the DMBA injection potently suppressed DMBA-induced CA, although its administration 2 h before did not. The suppression of DMBA-induced CA by Sudan III was observed at all periods after the DMBA treatment.…”

Section: Discussionmentioning

confidence: 96%

Suppressive effect of (-)-epigallocatechin gallate on 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells

Ito¹

2005

Environ. Mutagen Res.

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The suppressive effect of (-)-epigallocatechin gallate (EGCG), the major polyphenolic constituent present in green tea, on 7,12-dimethylbenz [a]anthracene (DMBA)-induced chromosome aberrations (CA) in rat bone marrow cells was studied. Rats given EGCG before the DMBA injection displayed a considerably suppressed frequency of DMBA-induced CA in their bone marrow cells. The suppressive effect of EGCG (60 mg/kg body weight) given 24 h before was observed 24, 30, 48 and 72 h after the DMBA injection, but not at the early period (6, 12 and 18 h) after the DMBA treatment. On the other hand, EGCG (60 mg/kg body weight) given 0.5 h before DMBA suppressed DMBA-induced CA at all periods after the DMBA injection. The suppression of EGCG given 24 h or 0.5 h before was observed for all doses of DMBA (25, 50, 75 and 100 mg/kg) investigated. EGCG given at 60 mg/kg body weight 0.5 h before the DMBA injection showed greater suppressive effect than the same dose given 24 h before. The suppressive effect of EGCG given 0.5 h before was dosedependent in the range of 20 60 mg/kg body weight. Methyl methanesulfonate (MMS: direct-acting carcinogen)-induced CA were not suppressed by EGCG.The administration of dehydroepiandrosterone (DHEA), a typical substrate for hydroxysteroid sulfotransferases, 0.5 h before DMBA injection also significantly suppressed DMBA-induced CA but DHEA given 24 h before did not.These results suggest that EGCG has two different suppression mechanisms for DMBA-induced CA depending on the administration time. The suppression of DMBA-induced CA by EGCG given 24 h or 0.5 h before may result from the modification of microsomal enzyme system or the inhibition of sulfotransferase activity by EGCG, respectively. We have previously reported (Ito et al., 1989) that the administration of GTE or GTP mixture before aflatoxin B 1 (AFB 1 ) injection in rats significantly suppressed AFB 1 -induced chromosome aberrations (CA) in bone marrow cells. Furthermore, we have reported (Ito and Ito, 2001) the suppressive effect of EGCG on AFB 1 -induced CA in rat bone marrow cells. EGCG given 24 h before the AFB 1 injection suppressed AFB 1 -induced CA but not when given 2 h before; the same was true for GTE or GTP mixture. This suppression seems to be due to modification of the microsomal enzyme system by EGCG.In this study, we investigated the suppressive effect of EGCG on CA induced by 7,12-dimethylbenz[a]anthracene (DMBA: indirect-acting carcinogen, as is AFB 1 ) and by methyl methanesulfonate (MMS: direct-acting carcinogen, needs no metabolic activation). Materials and Methods ChemicalsEGCG was purchased from Kurita Kogyo Co. (Tokyo, Japan). DMBA, dehydroepiandrosterone (DHEA) and colchicine were obtained from Wako Pure Chemicals Co. (Tokyo, Japan), MMS was from Aldrich (Milwaukee, WI), and dimethyl fulfoxide (DMSO: spectrophotometric grade) was from E. Merck A.G., (Darmstadt, F.R.G.). Animal experimentsMale rats of the Wistar strain (Charles River Japan, Inc., Kanagawa, Japan), aged 28 35 days and weighing 80 110 g, were used. Each...

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Section: Discussionmentioning

confidence: 96%

Suppressive effect of (-)-epigallocatechin gallate on 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells

Ito¹

2005

Environ. Mutagen Res.

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“…These include inbred strains that spontaneously develop cancer (1)(2)(3)(4), rodents in which cancer is caused by intrauterine or postnatal exposure to chemical mutagens (5)(6)(7)(8)(9), and mice in which tumors are produced by viral or bacterial infection (10)(11)(12)(13). In addition, xenograft models that were generated by directly implanting cancer cell lines established from human tumors into mice have been widely used for drug discovery (14)(15)(16)(17).…”

Section: Preclinical Mouse Models Of Human Cancermentioning

confidence: 99%

Harnessing preclinical mouse models to inform human clinical cancer trials

Gutmann

Hunter-Schaedle

Shannon

2006

Journal of Clinical Investigation

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The urgent need for better cancer treatments has stimulated interest in employing small-animal models to evaluate potential drug therapies. Robust mouse models of many human cancers have been generated using sophisticated technologies for engineering germ-line mutations. As we enter into an age of targeted therapeutics, these strains provide novel platforms for validating new anticancer drugs, assessing therapeutic index, identifying surrogate markers of tumor progression, and defining epigenetic and environmental influences on tumorigenesis.The availability of strains of genetically engineered mice (GEM) that develop a spectrum of cancers similar to those found in humans offers an unprecedented opportunity to efficiently evaluate the efficacy and therapeutic index of novel anticancer therapies in preclinical models in advance of human trials. While straightforward in principle, executing preclinical studies in mice that allow for meaningful and immediate application to the treatment of human cancer is difficult. Moreover, the potential use of GEM cancer models to accelerate the process of bringing effective new treatments to patients is largely theoretical, as few examples exist in which mouse preclinical data has been successfully translated to clinical practice. The current development process for anticancer drugsTaking a drug from discovery to market is an arduous process that frequently takes longer than 15 years and costs more than $800 million. Most agents that are advanced into early-phase human clinical trials fail. Recent advances in the fields of cancer biology and high-throughput screening have identified numerous potential molecular targets for drug discovery; however, most of the proteins and pathways deregulated in cancer cells also have essential roles in normal cells. It is therefore difficult to predict when a drug will prove tumor-selective. Moreover, developing new therapies against specific molecular abnormalities in well-defined subsets of cancers can be prohibitively expensive. The use of GEM cancer models as an initial "filter" to identify tumors and molecular targets that, when inhibited, will selectively kill tumor cells is one potential strategy for streamlining the overall process of cancer drug development. Preclinical mouse models of human cancerNumerous small-animal models of human cancer have been generated. These include inbred strains that spontaneously develop cancer (1-4), rodents in which cancer is caused by intrauterine or postnatal exposure to chemical mutagens (5-9), and mice in which tumors are produced by viral or bacterial infection (10-13). In addition, xenograft models that were generated by directly implanting cancer cell lines established from human tumors into mice have been widely used for drug discovery (14-17). The major limitations of these explant models are the requirement for an immunocompromised host and the inability of these models to fully recapitulate the complex relationship between the tumor and its microenvironment (e.g., angiogenesis). Most importan...

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“…Only a small number of PAHs, which belong to the bicyclics or tricyclics (naphthalene, fluorene, and some methylated congeners of phenanthrene, fluorene and anthracene), 22,30,32 or which show extremely poor solubility (2,6-dimethylpyrene 39 ) were negative in all studies and under all conditions used. Likewise, direct mutagenic effects to S. typhimurium strains were only reported for a few PAHs: 1,2,3,4-tetrahydro-DMBA, 26 1,2-dihydro-DMBA, 26 6,7,8,9,10, nb-hexahydro-S-MC, 24 2-methylanthracene, 43 9,10-dimethylanthracene, 34 tetracene 43 and benzo [4,5]cyclohept-[l,2,3-&c]acenaphthylene. 27 It is difficult to rule out that impurities or photoactivation were involved in some of these effects.…”

Section: In Vitro Mutagenicity Tests Using Bacterial Target Cellsmentioning

confidence: 99%

“…1,2 7,12-Dimethylbenz[a]anthracene (DMBA) and 3-methylcholanthrene (3-MC) are still widely used to induce tumors in certain tissues, such as skin, lung, mammary gland, large intestine and the hemopoietic system, [3][4][5][6][7][8] in order to study the individual steps of carcinogenesis or to find preventive factors.…”

Section: Introductionmentioning

confidence: 99%

Indicator Assays for Polycyclic Aromatic Hydrocarbon-Induced Genotoxicity

Glatt

2005

The Carcinogenic Effects of Polycyclic Aromatic Hydrocarbons

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7,12-DMBA-induced rat leukemia: a review with insights into future research

Cited by 34 publications

References 86 publications

Suppressive effect of (-)-epigallocatechin gallate on 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells

Suppressive effect of (-)-epigallocatechin gallate on 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells

Harnessing preclinical mouse models to inform human clinical cancer trials

Indicator Assays for Polycyclic Aromatic Hydrocarbon-Induced Genotoxicity

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