Chronic dietary toxicity and carcinogenicity studies of dammar resin in F344 rats
Chronic dietary toxicity and carcinogenicity studies of dammar resin in F344 rats
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达玛树脂对 F344 大鼠的慢性膳食毒性和致癌性研究
DOI：
10.1007/s00204-018-2316-7
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发表时间：
2018
影响因子：
6.1
通讯作者：
Wanibuchi Hideki
中科院分区：
文献类型：
--
作者：
Gi Min;Fujioka Masaki;Yamano Shotaro;Kakehashi Anna;Oishi Yuji;Okuno Takahiro;Yukimatsu Nao;Yamaguchi Takashi;Tago Yoshiyuki;Kitano Mistuaki;Hayashi Shim-mo;Wanibuchi Hideki
达玛树脂是一种天然食品添加剂和调味物质，存在于许多食品和饮料中。本研究评价了饲料达玛树脂对F344大鼠的慢性毒性和致癌性。52周慢性毒性研究中的饲料浓度为0、0.03、0.125、0.5或2%。主要给药相关有害作用为雄性和雌性动物的体重抑制、相对肝脏重量增加和血红蛋白水平降低。在雄性2%组中观察到肝脏细胞改变灶，但在任何其他组中均未观察到。慢性毒性的无明显不良作用水平为0.125%（200.4 mg/kg b.w./天）和雌性（241.9 mg/kg b.w./天）。104周致癌性研究中的膳食浓度为0、0.03、0.5或2%。达玛树脂诱导雄性和雌性动物的出血素质，可能通过抑制外源性和内源性凝血途径。在2%的男性组中，肝细胞腺瘤和癌的发生率显著增加，但在任何其他组中均未增加。在为期4周的亚急性毒性研究中，喂食含2%达玛树脂的饲料的雄性大鼠肝脏的蛋白质氧化水平升高，两种抗凋亡基因和七种细胞色素P450（CYP 14）基因的表达增加。DNA氧化损伤也有增加的趋势。这些研究结果表明，达玛树脂是在雄性F344大鼠肝癌，并强调的作用，抑制细胞凋亡，诱导酶，氧化应激在达玛树脂诱导的肝癌。
Dammar resin is a natural food additive and flavoring substance present in many foods and drinks. The present study evaluates the chronic toxicity and carcinogenicity of dietary dammar resin in F344 rats. Dietary concentrations in the 52-week chronic toxicity study were 0, 0.03, 0.125, 0.5, or 2%. The major treatment-related deleterious effects were body weight suppression, increased relative liver weight, and low hemoglobin levels in males and females. Foci of cellular alteration in the liver were observed in the male 2% group, but not in any other group. The no-observed-adverse-effect level for chronic toxicity was 0.125% for males (200.4 mg/kg b.w./day) and females (241.9 mg/kg b.w./day). Dietary concentrations in the 104-week carcinogenicity study were 0, 0.03, 0.5, or 2%. Dammar resin induced hemorrhagic diathesis in males and females, possibly via the inhibition of extrinsic and intrinsic coagulation pathways. Incidences of hepatocellular adenomas and carcinomas were significantly increased in the male 2% group, but not in any other group. In the 4-week subacute toxicity study, the livers of male rat-fed diet-containing 2% dammar resin had increased levels of protein oxidation and increased the expression of two anti-apoptotic and seven cytochrome P450 (CYP) genes. There was also an increased tendency of oxidative DNA damage. These findings demonstrate that dammar resin is hepatocarcinogenic in male F344 rats and underlines the roles of inhibition of apoptosis, induction of CYP enzymes, and oxidative stress in dammar resin-induced hepatocarcinogenesis.
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发表时间：
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