Screening Environmental Chemical Mixtures for Effects on Prostate Cancer Invasion Properties

EPA Grant Number: R827152
Title: Screening Environmental Chemical Mixtures for Effects on Prostate Cancer Invasion Properties
Investigators: Lindholm, Paul F. , Kajdacsy-Balla, Andre
Institution: Medical College of Wisconsin
EPA Project Officer: Fields, Nigel
Project Period: November 15, 1998 through November 14, 2001
Project Amount: $555,000
RFA: Chemical Mixtures in Environmental Health (1998) RFA Text |  Recipients Lists
Research Category: Hazardous Waste/Remediation , Health Effects , Land and Waste Management , Health , Safer Chemicals

Description:

The goals of this project are to test the hypothesis that complex environmental chemical mixtures are capable of inducing invasive properties in already established cancer cells, and to develop mechanism based methods for screening chemical mixtures for their ability to effect the expression of markers of metastatic disease in cancer cells. Apart from their carcinogenic properties, we hypothesize that complex chemical mixtures can activate latent, localized tumors to become invasive and metastatic. For example, smoking has been identified as a risk factor for worse clinical outcome in cancers of the prostate and other types of cancer, even when there is correction for grade and stage at diagnosis. Environmental factors must have a very important influence on tumor aggressiveness since the prevalence of prostate cancer is similar in Japanese and American populations while the mortality is almost five times greater for Americans and Japanese immigrants to America. Because cancer invasion and metastasis are the result of a multi-step process, it is likely that complex environmental factors will be more effective than a single chemical exposure for induction of invasive behavior in cancer cells.

Approach:

A major goal of this project is to identify reliable, high throughput assays which can measure the effect of complex chemical mixtures on prostate cancer progression such as the cDNA array test. PC-3 prostate cancer cells will be exposed to complex environmental chemical mixtures including cigarette smoke condensate, agricultural pesticides and heavy metals. Following the exposure, the cells will be analyzed by a battery of assays to determine whether they show changes that characterize aggressive cancer cells. Included are assays of invasion and adhesion to reconstituted basement membrane; the cDNA array test (a method to measure expression of multiple metastasis-associated genes in treated cells) and activation of the transcription factor NF-kappaB. This study will investigate additional chemical mixtures and prostate cancer cell lines to determine the general applicability of these in vitro approaches.

Expected Results:

The experimental design will identify efficient screening methods for determining the effect of complex environmental chemical mixtures on prostate cancer progression. Preliminary evidence indicates that cigarette smoke condensate and cadmium chloride cause increased invasive behavior of prostate cancer cells and increased expression of metastasis-associated genes. The screening methods should identify chemical mixtures that impact on prostate cancer progression and will be useful for further epidemiological and biological studies.

Publications and Presentations:

Publications have been submitted on this project: View all 7 publications for this project

Supplemental Keywords:

complex chemical mixtures, prostate cancer, invasion, metastasis, multi-step tumor progression, screening methods, high throughput, cDNA arrays, cadmium, cigarette smoke, agricultural pesticides, herbicides, pyrethroids, rural air, dioxin, emission source pollution, endosulfan, alachlor, atrazine., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, Toxics, ENVIRONMENTAL MANAGEMENT, Waste, air toxics, Environmental Chemistry, Health Risk Assessment, Epidemiology, pesticides, chemical mixtures, Risk Assessments, Physical Processes, Molecular Biology/Genetics, cancer risk, Risk Assessment, complex mixtures, effects assessment, exposure and effects, cell biology, emission source pollution, exposure, invasice properties, carcinogens, characterizing chemical mixtures, human exposure, epidemiological studies, atrazine, cadmium, cancer risk assessment, tobacco smoke, prostate cancer, exposure assessment, carcinogenic, Endosulfan Sulfate

Progress and Final Reports:

1999 Progress Report