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- W2904285020 abstract "Abstract Sulfotransferase 1A (SULT1A) expression is lower in the liver of humans than that of rodents. Therefore, species differences should be taken into consideration when assessing the risk of rodent hepatocarcinogens metabolically activated by SULT1A in humans. Although some renal carcinogens require SULT1A‐mediated activation, it is unclear how SULT1A activity in the liver affects renal carcinogens. To explore the effects of SULT1A activity in the liver on genotoxicity induced by SULT1A‐activated renal carcinogens, B6C3F 1 mice or gpt delta mice of the same strain background were given lucidin‐3‐ O ‐primeveroside (LuP), a hepatic and renal carcinogen of rodents, for 4 or 13 weeks, respectively, and pentachlorophenol (PCP) as a liver‐specific SULT inhibitor, was given from 1 week before LuP treatment to the end of the experiment. A 4 week exposure of LuP induced lucidin‐specific DNA adduct formation. The suppression of Sult1a expression was observed only in the liver but not in the kidneys of PCP‐treated mice, but co‐administration of PCP suppressed LuP‐induced DNA adduct formation in both organs. Thirteen‐week exposure of LuP increased mutation frequencies and cotreatment with PCP suppressed these increases in both organs. Given that intact levels of SULT activity in the liver were much higher than in the kidneys of rodents, SULT1A may predominantly activate LuP in the liver, consequently leading to genotoxicity not only in the liver but also in the kidney. Thus, species differences should be considered in human risk assessment of renal carcinogens activated by SULT1A as in the case of the corresponding liver carcinogens." @default.
- W2904285020 created "2018-12-22" @default.
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- W2904285020 date "2018-12-12" @default.
- W2904285020 modified "2023-10-18" @default.
- W2904285020 title "Effects of inhibition of hepatic sulfotransferase activity on renal genotoxicity induced by lucidin‐3‐ <i>O</i> ‐primeveroside" @default.
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- W2904285020 doi "https://doi.org/10.1002/jat.3755" @default.
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