transplacental carcinogenic promoting activity of chloroacetonitrile the role of L-ornithine and its relation to glutathione content in embryonic tissue

ABSTRACT

The possible transplacental carcinogenic promoting activity of chloroacetonitrile [CAN, a by-product of drinking water chlorination process] in timed pregnant mice was studied. The activity was investigated through the assessment of the embryonic ornithine-decarboxylase [ODS] activity in relation to the embryonic glutathione [GSH] content after maternal administration of CAN. CAN was administered orally in a single dose of 25, 50, 70, 100 and 150 mg/kg diluted in 0.2 ml corn oil to the pregnant mice [GD 11.5]. All mice were killed 2 hours after treatment and the embryonic tissue was prepared for analysis. Also, a time course study protocol was studied, CAN was given in a single oral dose of 25 or 75 mg/kg to the pregnant mice and they were killed at 2, 6, 12, 24 and 48 hours post-treatment at GD 11.5. Maternal administration of CAN in doses of 25, 50, 75 mg/kg produced a marked increase in ODC activity expressed as pmole 14CO2/mg protein/30 min., associated with a significant reduction in GSH content. However, treatment with CAN either in a dose of 100 or 150 mg/kg showed significant reductions in ODC activity and GSH content. Concerning time-course study protocol, maternal administration of CAN either in 25 or 75 mg/kg produced a significant increase in the embryonic ODC activity accompanied with a remarkable decrease in GSH content measured at 2, 6, 12, 24 and 48 hours post-maternal treatment. The increase in the embryonic carcinogenic marker ODC which was associated with GSH depletion after administration of non-cytotoxic doses of CAN reflected an indication towards the mechanistic pathway of the transplacental carcinogenic promoting potential of CAN