As part of a program to evaluate long term genetic effects of opiate abuse and investigate amelioration with replacements or antagonists, a series of stress systems has been developed to test the capacity of the cell to handle potential mutagenic crises. Heroin addicts have an increased frequency of chromosome damage in unstressed leukocyte cultures and with the stress systems it can be shown that there is also a defect in their ability to repair far UV damage as measured by unscheduled DNA synthesis and an alteration in sister chromatid exchange response when stressed by UV and mitomycin C. The changes in UV induced DNA repair and chromosome aberrations were corrected after long term methadone maintenance. To further understand the implication of these findings studies are planned to evaluate repair of UV damage with a second assay system and also to use a chemical stress agent in place of UV. The rate at which methadone reverses both the biochemical and cytogenetic effects as measured with chemical and UV stresses will be determined and compared with the rates found for LAAM and naltrexone. These studies should be useful in determining the relative effectiveness of these treatment modalities at the genetic level. In conjunction with the in vivo experiments studies will also be initiated to attempt to reproduce these findings in vitro with fibroblast cultures to investigate the mechanism which produce these effects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA001451-16
Application #
3206916
Study Section
Sociobehavioral Subcommittee (DAAR)
Project Start
1976-09-30
Project End
1993-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
16
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Shafer, D A; Xie, Y; Falek, A (1994) Detection of opiate-enhanced increases in DNA damage, HPRT mutants, and the mutation frequency in human HUT-78 cells. Environ Mol Mutagen 23:37-44
Madden, J J; Ketelsen, D; Whaley, W L (1993) Morphine binding sites on human T lymphocytes. Adv Exp Med Biol 335:61-6
Oleson, D R; DeFelice, L J; Donahoe, R M (1993) Ethanol increases K+ conductance in human T-cells. Alcohol Clin Exp Res 17:604-9
Oleson, D R; DeFelice, L J; Donahoe, R M (1993) A comparison of K+ channel characteristics in human T cells: perforated-patch versus whole-cell recording techniques. J Membr Biol 132:229-41
Donahoe, R M; Falek, A; Madden, J J et al. (1991) Effects of cocaine and other drugs of abuse on immune function. Adv Exp Med Biol 288:143-50
Madden, J J; Falek, A (1991) The use of nonneuronal cells as an in vitro model system for studying the genetic component of cellular response to opiates and other drugs of abuse. J Addict Dis 10:229-38
Donahoe, R M (1990) Immune effects of opiates in test tubes and monkeys. NIDA Res Monogr 105:89-95
Madden, J J; Falek, A; Donahoe, R et al. (1990) Opiate binding sites on cells of the immune system. NIDA Res Monogr 105:103-8
Shafer, D A; Dunbar, V G; Falek, A et al. (1990) Enhanced assays detect increased chromosome damage and sister-chromatid exchanges in heroin addicts. Mutat Res 234:327-36
Donahoe, R M (1990) Drug abuse and AIDS: causes for the connection. NIDA Res Monogr 96:181-91

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