Covalent binding of agaritine to DNA in vivo.
14C-Ring-labelled agaritine was administered orally to eight C57BL/6 mice at a chemical dose of 7.5 mg and radioactive dose of 1.2 x 10(9) dpm/kg body weight. After 24 hr, the animals were killed and DNA from stomach, liver and kidneys was purified by a phenol-free method involving proteinase K digestion of chromatin and coprecipitated proteins, followed by hydroxylapatite chromatography, dialysis and precipitation with ethanol. An increase in radioactivity was found in DNA of all three organs examined. Stomach DNA had the highest levels: 160 and 30 dpm/mg DNA in males and females, respectively. Liver and kidney DNA both showed levels of approximately 1 dpm/mg, with no measurable gender differences. Expressed in the units of the covalent binding index (CBI), agaritine has a potency of 42 in mouse stomach in males and 8 in females. The CBI of agaritine in liver and kidney was 0.2-0.3 in both sexes. The genotoxic activity of agaritine is thus very weak. The cumulative lifetime cancer risk of agaritine consumption in mushrooms is estimated to lie at approximately 10(-5).
Shephard
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Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Schlatter
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D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010659:Phenylhydrazines / Q000008:administration & dosage / Q000378:metabolism*; D012737:Sex Factors
D002250:Carbon Radioisotopes; D018736:DNA Adducts; D010659:Phenylhydrazines; D004247:DNA; C015654:agaritine