heroin and Neuroblastoma

The present study was undertaken to compare the neurotoxic effects of three etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of oripavine) and heroin with their ability to activate opiate receptors in human neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines. Neurotoxicity was measured by using [3H]-thymidine incorporation analysis, cell viability measurement and Cytosensor microphysiometry. It was found that, in spite of the very similar molecular structures of these opiates, they displayed significant differences in cytotoxicity, with etorphine and another derivative of oripavine possessing high potency but dihydroetorphine and heroin little effect. However, neurotoxic potency of the opiates was not directly correlated to their ability to activate opioid receptors, as determined by [35S]-guanylyl-5'-O-(gamma-tho)-triphosphate binding assay. These findings provide clear evidence of differential neurotoxicity of etorphine-like opiates, and suggest that the neurotoxicity is not closely related to the molecular configuration required as opioid receptor agonist but is probably associated with the presence of a double bond in the structure.

Topics: Animals; Cell Survival; Etorphine; Guanosine 5'-O-(3-Thiotriphosphate); Heroin; Humans; Narcotics; Neuroblastoma; Neurotoxins; PC12 Cells; Rats; Receptors, Opioid; Structure-Activity Relationship; Thebaine; Tumor Cells, Cultured

Topics: Animals; Cell Differentiation; Cell Division; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Dose-Response Relationship, Drug; Heroin; Mice; Mitosis; Naloxone; Neuroblastoma

Topics: Animals; Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Heroin; Male; Mice; Mice, Inbred A; Naloxone; Neuroblastoma; Time Factors

The effect of heroin on tumor growth and survival time was studied in mice with neuroblastoma. Daily SC injections of either 3, 6, 10, 15 mg/kg heroin were initiated either 2 weeks prior to tumor cell inoculations (pre-treated groups) of 10(6) S20Y cells or one week after tumor transplantation (post-treated groups); control animals received saline injections prior to tumor cell inoculation (saline-tumor group). Heroin administration that began prior to tumor cell inoculation was effective in inhibiting tumor growth and prolonging life-span at all dosages utilized, but a dose-related response was not observed. A prolongation in mean survival time of 32-39% and median survival time of 8-50% was found in tumor-bearing animals of the pre-treated groups in comparison to mice in the saline-tumor group. Tumor growth was retarded in mice pre-treated with heroin, but mean tumor size of these animals was comparable to controls on the day of death. Only one post-treated group, 6 mg/kg, was observed to have alterations in tumor growth and survival time. Heroin's action in retarding tumor growth and prolonging life-span was blocked by concomitant of an opiate antagonist (naloxone, 10 mg/kg). These results suggest that, in addition to heroin's analgesic and behavioral properties, this opiate may have an even greater biologic significance by modulating neoplasia.

Topics: Animals; Clone Cells; Dose-Response Relationship, Drug; Heroin; Injections, Subcutaneous; Male; Mice; Mice, Inbred A; Mitosis; Naloxone; Neoplasm Transplantation; Neoplasms, Experimental; Neuroblastoma