Cellular and biochemical aspects of growth retardation in rat fetuses induced by maternal administration of selected anticancer agents.
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.
D000818:Animals; D001834:Body Water / Q000032:analysis; D001835:Body Weight; D002452:Cell Count; D002467:Cell Nucleus / Q000032:analysis; D004247:DNA / Q000032:analysis / Q000037:antagonists & inhibitors; D003606:Dacarbazine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005865:Gestational Age; D007093:Imidazoles / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D011247:Pregnancy; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D051381:Rats; D014226:Triazenes / Q000494:pharmacology*
D007093:Imidazoles; D009588:Nitrogen Mustard Compounds; D011506:Proteins; D014226:Triazenes; D012313:RNA; D003606:Dacarbazine; D004247:DNA