Ehrich M, Jortner B S, Taylor D, Dunnington E A, Siegel P B
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061.
J Toxicol Environ Health. 1993 Aug;39(4):539-53. doi: 10.1080/15287399309531770.
The influence of genotypes of the major histocompatibility complex (MHC) on susceptibility to acute and delayed effects of an organophosphorus ester was measured in adult White Leghorn chickens from lines differing in response to sheep red blood cell (SRBC) antigen. Chickens from lines selected for high (HA) or low (LA) antibody response to SRBC and homozygous for B13B13 or B21B21 genotypes at the MHC were administered a single subcutaneous injection of diisopropyl phosphorofluoridate (DFP) at dosages of 0, 0.25, 0.50, or 1.0 mg/kg body weight using corn oil as the carrier. Criteria for toxicological responses included clinical, biochemical, and pathological measures. Clinical signs of acute cholinergic poisoning and delayed neuropathy were dose related. Brain and blood cholinesterase and carboxylesterase activities were more sensitive to inhibition by DFP than were liver cholinesterase and carboxylesterase activities. Cholinergic signs 3 h after administration of DFP were more pronounced in line HA than in line LA chickens. Pathological evidence of delayed neuropathy 2 wk after DFP administration was also more evident in HA than LA chickens. Although less pronounced than that for lines, differences in neurotoxic manifestations following DFP administration were greater for chickens of B21B21 than B13B13 genotypes. Activity of A-esterases, which hydrolyze organophosphorus esters without being inhibited by them, was lower in plasma of line HA than line LA chickens. Differences among the genotypes in activity of other esterases were not found in chickens not receiving DFP. These results indicated that responses of chickens to the neurotoxicant DFP were influenced by the background genome of the chickens.
在对绵羊红细胞（SRBC）抗原反应不同的成年白来航鸡品系中，测定了主要组织相容性复合体（MHC）基因型对有机磷酸酯急性和迟发效应易感性的影响。从对SRBC抗体反应高（HA）或低（LA）的品系中选取的鸡，在MHC处为B13B13或B21B21基因型纯合子，以玉米油为载体，分别以0、0.25、0.50或1.0mg/kg体重的剂量皮下注射一次二异丙基氟磷酸酯（DFP）。毒理学反应的标准包括临床、生化和病理学指标。急性胆碱能中毒和迟发性神经病变的临床体征与剂量相关。脑和血液中的胆碱酯酶及羧酸酯酶活性比肝脏中的胆碱酯酶和羧酸酯酶活性对DFP抑制更敏感。DFP给药3小时后的胆碱能体征在HA品系鸡中比在LA品系鸡中更明显。DFP给药2周后迟发性神经病变的病理学证据在HA品系鸡中也比在LA品系鸡中更明显。虽然不如品系间差异明显，但DFP给药后神经毒性表现的差异在B21B21基因型鸡中比在B13B13基因型鸡中更大。水解有机磷酸酯而不被其抑制的A酯酶活性在HA品系鸡血浆中比在LA品系鸡血浆中低。在未接受DFP的鸡中未发现其他酯酶活性在基因型间存在差异。这些结果表明，鸡对神经毒物DFP的反应受鸡的背景基因组影响。
