Chaube S, Swinyard C A
Teratology. 1975 Dec;12(3):259-70. doi: 10.1002/tera.1420120307.
Single ip injections of 600 mg/kg 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DIC) and 900 mg/kg 5-[3,3-bis(2-chlorethyl)-1-triazeno]-imidazole-4-carboxamide (BIC) were given to pregnant Wistar rats at day 12 and the animals were killed 4 h after injection and at days 13-17 of gestation. Fetal tissues were used to determine total DNA, RNA, and protein and the data used to derive cell number and cell weight, RNA, and protein/cell. Both compounds reduced total fetal body weight, DNA, RNA, and protein but reduction of RNA by BIC was not statistically significant. These effects were observed 4 h after injection, increased with age (days 13-17), and were 3-4 times greater for DIC than BIC. By using the value of 6.2 mumug DNA/cell, cell number and per-cell values for weight, RNA, and protein, and weight: DNA, RNA:DNA, and protein:DNA ratios were computed. The per-cell values and ratios in the DIC-exposed animals were 8-44% greater and in BIC-treated animals 0-11% greater than control animals of the same gestational age. Percentage of body water was the same in the experimental and control animals. The differences in DNA, RNA, and protein are believed to be related to drug-induced growth retardation incident to total fetal DNA reduction resulting in diminished cell number.
在妊娠第12天，给怀孕的Wistar大鼠单次腹腔注射600mg/kg的5-(3,3-二甲基-1-三氮烯基)-咪唑-4-甲酰胺（DIC）和900mg/kg的5-[3,3-双(2-氯乙基)-1-三氮烯基]-咪唑-4-甲酰胺（BIC），注射后4小时以及妊娠第13 - 17天处死动物。用胎儿组织测定总DNA、RNA和蛋白质，并将数据用于计算细胞数量、细胞重量、RNA以及蛋白质/细胞。两种化合物均降低了胎儿总体重、DNA、RNA和蛋白质，但BIC对RNA的降低在统计学上不显著。这些效应在注射后4小时即可观察到，随年龄增长（第13 - 17天）而增加，且DIC的效应比BIC大3 - 4倍。通过使用6.2μg DNA/细胞的值，计算细胞数量以及每个细胞的重量、RNA和蛋白质的值，还有重量:DNA、RNA:DNA和蛋白质:DNA的比率。与相同胎龄的对照动物相比，暴露于DIC的动物每个细胞的值和比率高8 - 44%，接受BIC处理的动物高0 - 11%。实验动物和对照动物的身体水分百分比相同。DNA、RNA和蛋白质的差异被认为与药物诱导的生长迟缓有关，这是由于胎儿总DNA减少导致细胞数量减少所致。
