The metabolism : sister chromatid exchanges and macromolecular binding of benzo[a]pyrene by mouse hepatoma cells in culture

Author

Eugene Leonard Schaefer

Date of Award

8-1985

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Sciences

Major Professor

James K. Selkirk

Committee Members

Sankar Mitra, Stephen J. Kennel, Peter A. Lalley

Abstract

A basic problem in cancer research is that individual humans and animals vary in susceptibility to initiation of cancer by carcinogens. Animals are used as test subjects in laboratory studies of cancer. However, animals are complex systems. Simpler systems such as animal cells in culture have been devised for the investigation of mechanisms of carcinogenesis. In the present research, the metabolism and some biological effects of the chemical carcinogen benzo[aa]P) were studied in a parent mouse hepatoma cell line, Hepa-1c1c7, and three of its variants, BP^rcl, MUL12, and TA0clBP^rcl. The goal of this research was to see if biochemical and biological differences could be detected among subpopulations of a supposedly homogeneous population of cells. The study of metabolism was emphasized because it is thought that the metabolism of B[a]P is a prerequisite for other biological effects of B[a]P.

BP,sup>r<.sup>cl metabolized B[a]P at a very low rate. Hepa-1c1c7 and MUL12 had high metabolic activity toward B[a]P. TA0clBP^rcl expressed intermediate metabolic activity which depended on culture conditions. Sister chromatid exchanges were induced by B[a]P in TA0clBP^rcl but not in BP^rcl. Metabolites of B[a]P were bound to nuclear RNA, DNA, and protein in Hepa-1c1c7, MUL12, and TAOclBP^rcl, but not in BP^rc1. More B[a]P metabolites were bound to histones H3 and H2A in Hepa-1c1c7 and TAOclBP^rc1 than in MUL12. Hepa-1c1c7 had the shortest population doubling time. MUL12 had the lowest saturation density, Hepa-1c1c7 and TAOc1BPc1 reached intermediate levels, and BPcl had the highest. MUL12 had the largest modal chromosome number, 100, compared with 58, 57, and 57 for Hepa-1c1c7, TAOclBP^rl, and BP^rcl, respectively.

These results show that a cloned population of cells may be composed of subpopulations. The response of a cell population to B[a]P depends chiefly on the metabolic activities of these subpopulations.

Recommended Citation

Schaefer, Eugene Leonard, "The metabolism : sister chromatid exchanges and macromolecular binding of benzo[a]pyrene by mouse hepatoma cells in culture. " PhD diss., University of Tennessee, 1985.
https://trace.tennessee.edu/utk_graddiss/12628