The rat liver foci bioassay: I. Age-dependence of induction by vinyl chloride of ATPase-deficient foci

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Abstract
The age-dependence of the induction of pre-neoplastic enzyme-altered hepatic foci was investigated. Rats were exposed (8 h/day, 7 days/week) to 2000 p.p.m. vinyl chloride (VC) either ‘transplacentally’ (exposure of pregnant females), or immediately after birth for different time intervals (5, 11, 17, 47, 83 days) or from an age of 7 or 21 days onwards. The animals were then kept without further treatment; livers were evaluated for ATPase-deficient foci at the age of 4 months. ‘Transplacental’ exposure and exposure from day 1 through 5 caused no increase over controls in ATPase-deficient foci, probably due to the lack of hepatocellular proliferation and the low rate of VC metabolism at this developmental stage. However, fod area was steeply increased when newborn rats were exposed for 11 and 17 days; but this was not further enhanced by a 47- or 83-day exposure. Only a few ATPasedeflcient foci occurred when exposure started 21 days after birth. Exposure of adult rats did not result in more ATPasedeficient fod than were seen in untreated controls; control values could not be increased by a proceeding partial hepatectomy. The results indicate that the induction of pre-neoplastic hepatocellular lesions in rats by VC is restricted to a well defined period (˜day 7–21) in the early lifetime of the animals. This period of highest sensitivity is characterized by the beginning of rapid liver growth.