| Age-related differences in susceptibility to carcinogenesis: a quantitative analysis of empirical animal bioassay data. | |
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MedLine Citation:
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PMID: 15289159 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In revising cancer risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) analyzed animal cancer bioassay data over different periods of life. In this article, we report an improved analysis of these data (supplemented with some chemical carcinogenesis observations not included in the U.S. EPA's original analysis) and animal bioassay studies of ionizing radiation. We use likelihood methods to avoid excluding cases where no tumors were observed in specific groups. We express dosage for animals of different weights on a metabolically consistent basis (concentration in air or food, or per unit body weight to the three-quarters power). Finally, we use a system of dummy variables to represent exposures during fetal, preweaning, and weaning-60-day postnatal periods, yielding separate estimates of relative sensitivity per day of dosing in these intervals. Central estimate results indicate a 5- to 60-fold increased carcinogenic sensitivity in the birth-weaning period per dose divided by(body weight(0.75)-day) for mutagenic carcinogens and a somewhat smaller increase--centered about 5-fold--for radiation carcinogenesis per gray. Effects were greater in males than in females. We found a similar increased sensitivity in the fetal period for direct-acting nitrosoureas, but no such increased fetal sensitivity was detected for carcinogens requiring metabolic activation. For the birth-weaning period, we found an increased sensitivity for direct administration to the pups similar to that found for indirect exposure via lactation. Radiation experiments indicated that carcinogenic sensitivity is not constant through the "adult" period, but the dosage delivered in 12- to 21-month-old animals appears a few-fold less effective than the comparable dosage delivered in young adults (90-105 days of age). |
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Authors:
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Dale Hattis; Robert Goble; Abel Russ; Margaret Chu; Jen Ericson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Environmental health perspectives Volume: 112 ISSN: 0091-6765 ISO Abbreviation: Environ. Health Perspect. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-08-03 Completed Date: 2004-10-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0330411 Medline TA: Environ Health Perspect Country: United States |
Other Details:
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Languages: eng Pagination: 1152-8 Citation Subset: IM |
Affiliation:
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George Perkins Marsh Institute, Clark University, 950 Main Street, Worcester, MA 01610, USA. dhattis@aol.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Animals Biological Assay Carcinogens / adverse effects* Databases, Factual Female Humans Male Models, Theoretical* Neoplasms / etiology*, veterinary Radiation Injuries Reproducibility of Results Risk Assessment Sensitivity and Specificity Sex Factors United States United States Environmental Protection Agency Weaning |
| Chemical | |
Reg. No./Substance:
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0/Carcinogens |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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