You are here:
A BIOASSAY THAT IDENTIFIES POSTNATAL FUNCTIONAL DEFICITS IN MICE PRENATALLY EXPOSED TO XENOBIOTICS
Citation:
Chernoff, N, M B. Rosen, AND L. Hall. A BIOASSAY THAT IDENTIFIES POSTNATAL FUNCTIONAL DEFICITS IN MICE PRENATALLY EXPOSED TO XENOBIOTICS. Presented at Society of Toxicology, San Francisco, CA, March 25 - 29, 2001.
Description:
Experimental strategies to evaluate adverse postnatal effects due to prenatal exposure exist for many organ systems. Often, however, there is insufficient information to suggest that a particular organ system(s) may be sensitive to the test agent. A single bioassay to identify significant functional deficit(s) in a variety of organ systems would be useful in cases like this. We have assumed that adverse effects on organ systems will interfere with postnatal growth, and will be most readily identified when the systems are challenged. This potential bioassay monitors growth in large litters of mice (16 pups) which induces stress as a general challenge. The litters are composed of 8 randomly selected control and 8 treated pups (C X T litters) cross-fostered to control dams on postpartum day 1 (PD1). A common effect is reduced pup weight at birth and the bioassay has to distinguish between growth differences due to functional deficits and those related to initial weight differences. We therefore also create litters of 16 control pups (C X C litters) weight matched to control and exposed pups in the C X T litters. Growth and viability of the neonates are evaluated from birth through PD 27. The growth of the exposed pups in the C X T litters is compared to the control pups of equal initial weights in the C X C litters. Agents tested were 5-aza-2'-deoxycytidine (d-AZA) 0.33 and 0.17 mg/kg, i.p., gestation day (GD) 10; boric acid 500 mg/kg, gavage, GD6-8 or 6-10; and Na-salicylate 800 mg/kg, gavage, GD 6-15. All treatments caused weight reduction at birth. Of the compounds tested to date, only 0.33 mg/kg of d-AZA produced a significant growth decrement when compared to its weight matched control population indicating some organ system dysfunction interfering with growth in the exposed group. We conclude that this test may have promise as a means of identifying postnatal organ system dysfunction in those instances where target systems are unknown.
(This abstract does not necessarily reflect policy of the US EPA.)