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ANALYSES OF THE INTERACTIONS WITHIN BINARY MIXTURES OF CARCINOGENIC PAHS USING MORPHOLOGICAL CELL TRANSFORMATION OF C3H10T1/2CL8 CELLS
Citation:
Nesnow, S, C. Davis, M Pimentel, M J. Mass, G B. Nelson, AND J A. Ross. ANALYSES OF THE INTERACTIONS WITHIN BINARY MIXTURES OF CARCINOGENIC PAHS USING MORPHOLOGICAL CELL TRANSFORMATION OF C3H10T1/2CL8 CELLS. Presented at American Association of Cancer Research, New Orleans, LA, March 24-28, 2001.
Description:
ANALYSES OF THE INTERACTIONS WITHIN BINARY MIXTURES OF CARCINOGENIC PAHS USING MORPHOLOGICAL CELL TRANSFORMATION OF C3HIOT1/2 CL8 CELLS.
Studies of defined mixtures of carcinogenic polycyclic aromatic hydrocarbons (PAH) have identified three major categories of interactions: antagonism; synergism; and additivity depending on the biological model, tissue, route of exposure, and specific PAH. To understand the bases of these interactions we studied binary mixtures ofbenzo[a1pyrene (B[a]P) and dibenz[a,h]anthracene (DBA) in transformable C3HlOTYzCI8 (C3HJ OTYz) mouse embryo fibroblast cells in culture. C3HlOTYz cells were treated separately with B(a )P (0, 0.5, 1.0 ug/ml) or DBA (0, 0.5, 1.0 ug/ml) and with 1 :1, 1 :2 and 2:1 mixtures ofB[a]P and DBA for 24 hr and the dishes were scored 6 weeks later. Response surface methodology was applied to examine the changes in transformation frequency in quantitative terms over both B[a]P and DBA concentration ranges. C3HI0TY2 cells treated with binary mixtures ofB[a]P and DBA gave less than additive morphological cell transformation based on linear response additivity. For example, B[a]P (1.0 f.lg/ml) and DBA (1.0 ug/ml) gave transformation frequencies (Type II&III foci/surviving cell, TF) of 5.46 and 3.82 x 10-3 respectively. The mixture of B[a]P and DBA each at 1.0 f.lg/ml gave a TF of2.66 x 10-3. These results were consistent with those reported in mice and rats on the antagonistic effects ofB[a]P and DBA on umorigenesis. 32p-postlabeling DNA adduct studies revealed that DBA reduced B[a]P-DNA adduct levels by 47% with no effect on DBA-DNA adduct levels. This suggests that one mechanism for the inhibition of morphological cell transformation of binary mixtures ofB[a ]P and DBA is due to alterations in the metabolic activation ofB[a]P.
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