Connor M J, Puhvel S M, Sakamoto M, Nanthur J
Department of Medicine, UCLA School of Medicine 90024.
Arch Toxicol. 1994;69(2):87-90. doi: 10.1007/s002040050142.
In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 micrograms TCDD/kg body weight on postnatal day 0. At 12 micrograms/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 micrograms/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice.
在小鼠中，隐性突变无毛（hr）控制皮肤对2,3,7,8 - 四氯二苯并 - 对 - 二恶英（TCDD）的反应，但其对TCDD全身毒性的影响尚不清楚。为了阐明这一点，我们比较了哺乳期暴露于TCDD对标准化同窝新生HRS/J小鼠的影响，这些小鼠要么是hr纯合子，要么是 + 纯合子，由在出生后第0天暴露于0、6、8或12微克TCDD/千克体重的有毛母鼠哺育。在12微克/千克时，TCDD对有毛和无毛幼崽均致死。在较低剂量（6和8微克/千克）时，hr/hr幼崽的存活率显著低于 +/+ 幼崽。受影响的幼崽在1至2天的恶病质和消瘦期后死亡。正如其他小鼠品系所报道的那样，TCDD暴露影响了它们的新生儿发育，并缩短了有毛和无毛幼崽睁眼的时间。然而，无毛动物比有毛动物在更低剂量时就受到影响。这项研究的结果证明，hr/hr基因型确实会影响小鼠中TCDD的全身毒性。
