Arce D S, Keen C L
Biochemical Research and Development, Miles Inc., Berkeley, California 94701.
Reprod Toxicol. 1993;7(1):61-72. doi: 10.1016/0890-6238(93)90011-u.
Transferrin, metallothionein, cytochrome P-450, and the in vitro formation of DNA-benzo[a]pyrene adducts were studied in the offspring of dams that were fed diets moderately or severely deficient in iron (Fe). The study was designed to determine whether Fe deficiency-induced alterations were reversible or if they persisted with post-weaning iron repletion. Throughout gestation and lactation the dams were fed a Control diet = 120 micrograms Fe/g diet, a Marginal Iron diet = 11 micrograms Fe/g diet, or a Low Iron diet = 7 micrograms Fe/g diet. On day 14 of lactation, 4 pups per litter were killed. On day 21, the dams were killed. Half of the remaining pups in each litter were fed their respective diets until they were killed on day 42 (Marginal Iron-Marginal Iron and Low Iron-Low Iron groups). The other half were fed the Control diet (Marginal Iron-Control and Low Iron-Control groups). The dietary intake of the Restricted Fed offspring was matched to rats in the Low Iron-Low Iron group. Offspring in the iron-deficient groups had hematocrits, hemoglobin concentrations, and liver iron levels that were lower than Controls. Day 42 offspring in the iron-deficiency groups had a lower food intake and higher liver zinc and copper levels than Controls. Day 14 Marginal and Low Iron pups had liver metallothionein levels that were lower than Controls. Day 42 Restricted Fed offspring had liver metallothionein levels that were higher than all other groups. Cytochrome P-450 levels and the in vitro formation of benzo[a]pyrene-DNA adducts were higher in Low Iron-Low Iron males than in Control males. Ethoxycoumarin O-deethylase activity was higher in day 42 Low Iron-Low Iron offspring than in Controls. These results show that the iron deficiency-induced alterations were transient, reversible with iron repletion, and in the case of cytochrome P-450 and ethoxycoumarin O-deethylase activity, dependent on the age and sex of the animal.
对喂食铁(Fe)中度或严重缺乏日粮的母鼠后代的转铁蛋白、金属硫蛋白、细胞色素P - 450以及DNA - 苯并[a]芘加合物的体外形成进行了研究。该研究旨在确定铁缺乏诱导的改变是否可逆,或者在断奶后铁补充后是否持续存在。在整个妊娠和哺乳期,母鼠分别喂食对照日粮(120微克铁/克日粮)、边缘铁日粮(11微克铁/克日粮)或低铁日粮(7微克铁/克日粮)。在哺乳期第14天,每窝处死4只幼崽。在第21天,处死母鼠。每窝剩余幼崽的一半继续喂食各自的日粮,直至在第42天处死(边缘铁 - 边缘铁组和低铁 - 低铁组)。另一半喂食对照日粮(边缘铁 - 对照组和低铁 - 对照组)。限饲后代的日粮摄入量与低铁 - 低铁组的大鼠相匹配。缺铁组的后代的血细胞比容、血红蛋白浓度和肝脏铁水平低于对照组。缺铁组第42天的后代比对照组的食物摄入量低,肝脏锌和铜水平高。第14天的边缘铁和低铁幼崽的肝脏金属硫蛋白水平低于对照组。第42天限饲后代的肝脏金属硫蛋白水平高于所有其他组。低铁 - 低铁雄性小鼠的细胞色素P - 450水平和苯并[a]芘 - DNA加合物的体外形成高于对照雄性小鼠。第42天低铁 - 低铁后代的乙氧基香豆素O - 脱乙基酶活性高于对照组。这些结果表明,铁缺乏诱导的改变是短暂的,可通过铁补充逆转,并且就细胞色素P - 450和乙氧基香豆素O - 脱乙基酶活性而言,取决于动物的年龄和性别。