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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Dec;85(12):1220–1228. doi: 10.1111/j.1349-7006.1994.tb02933.x

Activation of 2‐Hydroxyamino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridne by cDNA‐expressed Human and Rat Arylsulfotransferases

Shogo Ozawa 1,✉, Hsien‐Chang Chou 2,†, Fred F Kadlubar 2, Kiyoshi Nagata 1, Yasushi Yaraazoe 1,‡, Ryuichi Kato 1
PMCID: PMC5919400  PMID: 7852185

Abstract

Sulfation plays an obligatory role in the activation of N‐hydroxy derivatives of carcinogenic aryl‐amiric(amide)s and heterocyclic amines. We found that the hepatic sulfotransferase‐mediated covalent binding of 3H‐labeled 2‐hydroxyamino‐1‐inethy1‐6‐phenylimidazo[4,5‐b]pyridine (N‐OH‐PhIP) to calf thymus DNA was 3.3 and 12.9 times higher with human cytosol preparation than with male and female rat cytosol preparations, respectively, in the presence of 3’‐phosphnadenosine 5’‐phospho‐sulfate. To assess the activating capacities of individual phenol‐sulfating sulfotransferascs, five different forms, human ST1A2 and ST1A3 and rat ST1A1, ST1B1 and ST1C1, were expressed in heterologous cells. All five sulfotransferases mediated the activation of N‐OH‐PhIP to DNA‐bound products. The extents of the binding, however, differed considerably among these forms. Human ST1A2 and ST1A3 mediated the activation of N‐OH‐PhIP at 5.2‐ and 6.2‐fold higher rates than did rat ST1C1, a main N‐hydroxy‐2‐acetylaminofluorene‐activating sulfotransferase, in rat liver. Extents of the binding of N‐OH‐PhIP in human hepatic cytosols of different individuals were positively correlated with the contents of immunoreactive ST1A2/3. These results suggest a potential role of human liver sulfotransferases in N‐OH‐PhIP activation. In contrast, the low sulfotransferase‐mediated activation of N‐OH‐PhIP in rat liver is consistent with the lack of PhIP hepatocarcino‐genicity in this species.

Keywords: Pyrolysate carcinogen, DNA binding, Human liver, Sulfation, cDNA expression

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