ABSTRACT
The aim of this study was to determine the frequency of sister-chromatid exchanges (SCEs) in heroin-cannabis, heroin and cannabis addicts. The group of 84 subjects consisted of 42 controls, 16 heroin-cannabis addicts, 12 heroin addicts and 14 cannabis addicts. The mean number of SCEs/cell was 12.95 in heroin-cannabis addicts, 12.05 in heroin addicts and 11.99 in cannabis addicts. These values are significantly (P less than 0.002) higher than the mean values found in controls. This increase in SCEs may be related to reduced DNA repair in chronic drug addicts, which would allow the fixation or retention of a greater fraction of the DNA lesions caused by normal environmental exposure.
Subject(s)
Heroin Dependence/genetics , Marijuana Abuse/genetics , Sister Chromatid Exchange , Adult , DNA Repair , Drug Interactions , Heroin Dependence/complications , Humans , Marijuana Abuse/complicationsABSTRACT
The effect of benzamide (B) and 3-aminobenzamide (3-AB) on sister chromatid exchanges (SCEs) and cell kinetics induced in vitro by melphalan (MELPH) or thiotepa (THIO) was studied in normal human lymphocytes. The combined treatments with either MELPH or THIO plus B or 3-AB showed the potentiating ability on SCE rates and the ability to induce cell division delays of the latter chemicals. In a combined in vivo and in vitro study, lymphocytes taken from six cancer patients who had been given cytoxan by injection 2 hr before and then treated with theophylline (THEOPH) or B or 3-AB in vitro were found to have synergistically increased exchange rates and cell division delays. The frequency of SCEs in the patients own lymphocytes with and without exposure to inhibitor of Poly(ADP-ribose) polymerase (P(ADPR)polymerase) was determined before the cytostatic therapy and was used as a control for later comparison in each individual case. These results further substantiate the use of this approach for detecting the induction of cytogenetic damage concerning controlled mutagen human exposure in combined in vivo and in vitro studies. Chemically induced cytotoxicity manifested as an alteration (division delay) in cell kinetics and as synergistic DNA damage by cytostatics and inhibitors of P(ADPR)polymerase may be of use in the treatment of human cancer.
Subject(s)
Benzamides/pharmacology , Lymphocytes/cytology , Melphalan/pharmacology , Mutagens , Poly(ADP-ribose) Polymerase Inhibitors , Sister Chromatid Exchange/drug effects , Thiotepa/pharmacology , Bromodeoxyuridine/pharmacology , Cell Division/drug effects , Colchicine/pharmacology , Drug Synergism , Humans , Kinetics , Lymphocytes/drug effectsABSTRACT
The effects of nicotinamide on SCE rates induced in vitro by chlorambucil (CBC or melphalan (MELPH) or mitomycin C (MMC) was studied. The combined treatments with either CBC or MELPH or MMC and nicotinamide showed the potentiating ability of the latter drug. Theophylline and MELPH were also found to act synergistically on the induction of SCEs. In a combined in vivo and in vitro study, lymphocytes taken from 7 cancer patients who had been given cytoxan by injection 3 h before, were treated with nicotinamide or diphylline (DP) in vitro, and found to have synergistically increased exchange rates. This has implications for interpreting the repair processes involved, for monitoring drug combinations that synergistically damage DNA in vivo and in vitro and for identifying interindividual variation in the response to the treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Lymphocytes/drug effects , NAD+ Nucleosidase/antagonists & inhibitors , Poly(ADP-ribose) Polymerase Inhibitors , Sister Chromatid Exchange/drug effects , DNA Repair/drug effects , Drug Synergism , Humans , In Vitro Techniques , Lymphocytes/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Niacinamide/pharmacology , Theophylline/pharmacologyABSTRACT
The effect of diphylline (DP) or (1,2-dihydroxy-3-propyl)-theophylline and theobromine (TB) on sister chromatid exchange (SCE) rates induced in vitro by cytosine arabinoside (AraC) was studied in normal human lymphocytes. The combined treatments with AraC plus DP or TB showed the potentiating ability of the latter drugs. In a combined in vivo and in vitro study, lymphocytes taken from 14 patients suffering from various types of cancer who had been given Cytoxan (5 patients) or AraC (9 patients) by injection 3 hr before and then treated with DP or TB in vitro were found to have synergistically increased exchange rates. This has implications for interpreting the repair processes involved and for monitoring drug combinations that synergistically damage DNA in vivo and in vitro.
