The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Original Article
Protective role of metallothionein in benzo[a]pyrene-induced DNA damage
Masaki TakaishiMasumi SawadaAkinori ShimadaJunko S. SuzukiMasahiko SatohHisamitsu Nagase
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ジャーナル フリー

2009 年 34 巻 5 号 p. 449-458

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Metallothionein (MT) is known to reduce chemical carcinogenesis. Carcinogenesis induced by benzo[a]pyrene (B[a]P) which is an environmental chemical carcinogen is related to DNA adduct formation and oxidative damage through metabolic activation. Ten-week-old male MT-I/II null mice and wild-type mice were given a single injection of B[a]P (250 mg/kg, p.o.), and B[a]P-induced DNA damage was evaluated at 6-48 hr later. The frequencies of micronucleated reticulocytes (MNRET) in MT-I/II null mice were significantly increased compared with that of wild-type mice at 48 hr after B[a]P administration. At 48 hr after B[a]P administration, comet scores were significantly increased in MT-I/II null mice but not in wild-type mice. 8-Hydroxy-2’-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, was significantly increased in liver of MT-I/II null mice at 6 and 12 hr after B[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, MT levels in the livers of wild-type mice were significantly increased by the B[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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© 2009 The Japanese Society of Toxicology
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