Accumulation of SCEs in lymphocytes during chronic ingestion of a mutagen.
Studies in 2 large-animal species have shown that continued ingestion of a mutagen increases sister chromatid exchanges (SCE) in circulating lymphocytes at rates directly related to the accumulated dose but differing between species. Groups of 3 pigs received daily oral doses of 0, 1.25, or 2.50 mg/kg body weight of 7,12-dimethylbenzanthracene (DMBA) for 160 consecutive da; similar groups of sheep received 0, 0.625, or 1.25 mg/kg daily for up to 114 da. Lymphocytes taken at 3-wk intervals from pigs and every 2 wk from sheep were cultured, and 25 randomly selected second-division metaphases from each culture were scored for SCE. Swine lymphocytes had elevated numbers of SCE at the earliest sampling times after DMBA feeding was begun. Sister chromatid exchanges continued to increase gradually among pigs consuming 1.25 mg/kg/da for 160 da whereas those on 2.5 mg/kg tended to plateau at approximately 2.5 times their pretreatment level after some 80 da. Sheep treated with comparable levels of DMBA (1.25 mg/kg) exhibited a much more rapid rise in SCE than pigs; within 40 da their SCEs were at 4 times the control level and animals were exhibiting toxicity symptoms. Low-dose sheep also showed a rapid initial increase but plateaued at about 2.5 times the control level beyond 40 da.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013552:Swine / Q000235:genetics; D013997:Time Factors
D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene