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. 1987 Dec;76:57–63. doi: 10.1289/ehp.877657

High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

J A Swenberg 1, F C Richardson 1, J A Boucheron 1, F H Deal 1, S A Belinsky 1, M Charbonneau 1, B G Short 1
PMCID: PMC1474488  PMID: 3447904

Abstract

Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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