Faculty Collaboration Database

Lung tumorigenic interactions in strain A/J mice of five environmental polycyclic aromatic hydrocarbons. Environ Health Perspect 1998 Dec;106 Suppl 6(Suppl 6):1337-46

Date

12/23/1998

Pubmed ID

9860890

Pubmed Central ID

PMC1533448

DOI

10.1289/ehp.98106s61337

Scopus ID

2-s2.0-0032449586 (requires institutional sign-in at Scopus site)   60 Citations

Abstract

The binary, ternary, quaternary, and quintary interactions of a five-component mixture of carcinogenic environmental polycyclic aromatic hydrocarbons (PAHs) using response surface analyses are described. Initially, lung tumor dose-response curves in strain A/J mice for each of the individual PAHs benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DBA), 5-methylchrysene (5MC), and cyclopenta[cd]pyrene (CPP) were obtained. From these data, doses were selected for the quintary mixture study based on toxicity, survival, range of response, and predicted tumor yields. The ratios of doses among PAHs were designed to simulate PAH ratios found in environmental air and combustion samples. Quintary mixtures of B[a]P, B[b]F, DBA, 5MC, and CPP were administered to male strain A/J mice in a 2(5) factorial 32-dose group dosing scheme (combinations of five PAHs each at either high or low doses) and lung adenomas were scored. Comparison of observed lung adenoma formation with that expected from additivity identified both greater than additive and less than additive interactions that were dose related i.e., greater than additive at lower doses and less than additive at higher doses. To identify specific interactions, a response surface analysis using response addition was applied to the tumor data. This response surface model contained five dose, ten binary, ten ternary, five quaternary, and one quintary parameter. This analysis produced statistically significant values of 16 parameters. The model and model parameters were evaluated by estimating the dose-response relationships for each of the five PAHs. The predicted dose-response curves for all five PAHs indicated a good estimation. The binary interaction functions were dominated for the most part by DBA and were inhibitory. The response surface model predicted, to a significant degree, the observed lung tumorigenic responses of the quintary mixtures. These data suggest that although interactions between PAHs do occur, they are limited in extent.

Author List

Nesnow S, Mass MJ, Ross JA, Galati AJ, Lambert GR, Gennings C, Carter WH Jr, Stoner GD

MESH terms used to index this publication - Major topics in bold

Adenoma
Animals
Carcinogens
Dose-Response Relationship, Drug
Lung Neoplasms
Male
Mice
Mice, Inbred A
Polycyclic Aromatic Hydrocarbons
Pyrenes
Surface Properties