N-alkyl-N-nitrosourea induced secondary structural changes in DNA from rat embryos and fetal brains in vivo.

摘要: N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) are gestational stage dependent teratogens transplacental carcinogens capable of inducing neurogenic tumours in rats. Intravenous treatment gravid Wistar rats showed that MNU is teratogenic but ENU a carcinogen may be teratogen when administered on day 12 gestation. Twenty-four hours after single doses 2, 5, or 10 mg MNU/kg 12, dose decreases embryonic wet weight total DNA were observed. Rats similarly treated with 2 5 fetal brain synthesis, content, 9 days later. Administration 1.5, 3, 6, 48, 80 mg/kg to embryos resulted reduction [methyl-14C]-thymidine (14C-TdR) incorporation into 24 h although amounts weights unaffected. Benzoylated DEAE-cellulose (BD-cellulose) chromatography fractionates the basis secondary structure by stepwise elution double-stranded 1.0 M NaCl solution (SE-DNA) followed containing single-stranded regions caffeine (CE-DNA). Day 13 21 was monitored vivo labelling [methyl-3H]-thymidine 6 7 Significant percentages CE-DNA (%CE-DNA) attributed necrotic effect MNU. produced no change %CE-DNA values brains. A ENU/kg significantly increased compared controls changes observed 1.5 48 mg/kg. Analysis distribution from litter increase due second distinct population higher than controls. Incorporation 14C-TdR demonstrated effects these compounds synthesis vivo. The relative expressed as ratio percentage caffeine-eluted 14C-labelled (i.e., %CE-14C-DNA:%CE-3H-DNA). In majority control 14C-specific activity SE-DNA.(ABSTRACT TRUNCATED AT 400 WORDS)