B cell lymphomas are characterized by mutations,chromosomal rearrangements and other genetic alterations. DNA damage repair mechanisms are postulated to be involved in the origin of some of these mutations and chromosomal translocations. This study aims at elucidating the normal and aberrant functions of a novel error prone DNA polymerase, Poll Mu, that is highly expressed in the germinal center B cells, as a possible mutagenic mechanism contributing to B cell lymphomas. To achieve this objective, we will use wild type and mutant forms of Pol Mu expressed in human cell lines. We will assess the results of Pol Mu overexpression in B cells, evaluating the effect on mutation frequency and response to DNA damage inducing cytotoxic drugs. We will also screen tissue samples from lymphoma patients for levels of Pol Mu expression. Finally, we will attempt to determine whether Pol Mu plays a role in the t(14;18) translocations commonly found in follicular lymphomas. These studies will determine whether Pol Mu expression plays a role in lymphomagenesis.
Archibeque-Engle, S; Tessari, J D; Winn, D T (1996) Quality assurance/quality control procedures for chlorinated hydrocarbons in human breast adipose tissue. J Toxicol Environ Health 49:589-98 |