Cytotoxicity of Diepoxybutane and Epichlorohydrin in Relation to Stages of the Cell Cycle

Work conducted in the Millard Biochemistry Research Laboratory examines the dual nature of molecules as carcinogens and anti-tumor agents through the molecular mechanisms of duplex DNA damage by bifunctional alkylating agents. Diepoxybutane (DEB) and epichlorohydrin (ECH) are polar molecules that form covalent DNA interstrand lesions by cross-linking the N7 position of deoxyguanosine residues. A recent experiment indicated that ECH preferentially targets nuclear DNA over mitochondrial DNA, whereas DEB shows similar rates of lesion formation for both loci. It was concluded that preferential targeting of nuclear DNA results from relatively poor uptake of ECH across the mitochondrial membrane. The objective of my honors research was to determine if the cytotoxicities of DEB and ECH vary according to the presence of the nuclear envelope in 6C2 chicken erythro-progenitor cells. The cytotoxicity of DEB and ECH was compared between cells randomly distributed throughout the cell cycle (Go/G, and S » G2/M) and cells enriched in G2/M stages. Results indicated that ECH is more cytotoxic than DEB in both unsynchronized control 6C2 cells and synchronized 6C2 cells enriched in G2/M stages of the cell cycle. Treatment with either bifunctional alkylating agent induced greater cytotoxicity in 6C2 cells enriched in G2/M stages than in unsynchronized control 6C2 cells, suggesting that the presence of the nuclear envelope-or any plasma membrane-may inhibit the reactivity of DEB and ECH.

Enforcement in environmental law: an economic analysis of citizen suits

Previous to 1970, state and federal agencies held exclusive enforcement responsibilities over the violation of pollution control standards. However, recognizing that the government had neither the time nor resources to provide full enforcement, Congress created citizen suits. Citizen suits, first amended to the Clean Air Act in 1970, authorize citizens to act as private attorney generals and to sue polluters for violating the terms of their operating permits. Since that time, Congress has included citizen suits in 13 other federal statutes. The citizen suit phenomenon is sufficiently new that little is known about it. However, we do know that citizen suits have increased rapidly since the early 1980's. Between 1982 and 1986 the number of citizen suits jumped from 41 to 266. Obviously, they are becoming a widely used method of enforcing the environmental statutes. This paper will provide a detailed description, analysis and evaluation of citizen suits. It will begin with an introduction and will then move on to provide some historic and descriptive background on such issues as how citizen suit powers are delegated, what limitations are placed on the citizens, what parties are on each side of the suit, what citizens can enforce against, and the types of remedies available. The following section of the paper will provide an economic analysis of citizen suits. It will begin with a discussion of non-profit organizations, especially non-profit environmental organizations, detailing the economic factors which instigate their creation and activities. Three models will be developed to investigate the evolution and effects of citizen suits. The first model will provide an analysis of the demand for citizen suits from the point of view of a potential litigator showing how varying remedies, limitations and reimbursement procedures can effect both the level and types of activities undertaken. The second model shows how firm behavior could be expected to respond to citizen suits. Finally, a third model will look specifically at the issue of efficiency to determine whether the introduction of citizen enforcement leads to greater or lesser economic efficiency in pollution control. The database on which the analysis rests consists of 1205 cases compiled by the author. For the purposes of this project this list of citizen suit cases and their attributes were computerized and used to test a series of hypotheses derived from three original economic models. The database includes information regarding plaintiffs, defendants date notice and/or complaint was filed and statutes involved in the claim. The analysis focuses on six federal environmental statutes (Clean Water Act} Resource Conservation and Recovery Act, Comprehensive Environmental Response Compensation and Liability Act, Clean Air Act, Toxic Substances Control Act, and Safe Drinking Water Act) because the majority of citizen suits have occurred under these statutes.