Clastogenic effects of heroin in pregnant monkeys and their offspring.

Heroin was administered daily i.v. to pregnant Macaca mulatta monkeys, for 3 months, and after birth of their babies, was continued for 3 months post-partum. The dose was gradually increased to as high as 1.5 mg/kg/day. Pregnant control animals were given saline injections following the same design. WBC cultures for analysis of sister-chromatid exchanges (SCEs) and chromosome aberrations were taken from all adult animals, prior to heroin or saline administration, and also after 6 months, at time of sacrifice. Cultures were also done for all babies, and bone marrow analyses of aberrations were done on all animals at sacrifice. Both heroin mothers and babies showed a doubling in SCE level over their respective controls, and the heroin mothers demonstrated an almost 3-fold increase over their initial cultures. Heroin babies had 10 times as many chromosome aberrations in their WBC cultures as did their controls, and an equivalent increase in their bone marrow cells. The heroin mothers' final WBC cultures showed an increase in chromosome aberrations both over that of their initial cultures and those of their controls. The heroin babies demonstrated greater sensitivity to heroin, compared with their mothers, as measured by chromosome aberrations, but a corresponding sensitivity to SCE induction. No correlation in SCE levels was detected between individual pairs of mothers and babies, but there was one between the groups of mothers and babies. The route(s) through which the chromosomal alterations were inflicted in the babies could be transplacental, through the mother's milk, or both. The results of this investigation correspond with those of several previous studies on addict populations, and demonstrate that under these conditions, heroin is a chromosomal mutagen.

The relevance of the structural co-factor (chemogenic lesion) in adverse and toxic reactions of neuropsychotropic agents.

1. Multidisciplinary methodologies in human and experimental investigations revealed that neuropsychotropic agents display multiple neural and extraneural "targets" or bioreceptors. 2. The adverse and toxic reactions would be, in essence, the expression of a reversible or irreversible "chemogenic lesion" resulting from the molecular interactions among the chemical agents and the morpho-chemical correlates of the organism at any level of the structural organization. 3. In pathogenic terms, this "chemogenic lesion" appears as a patho-chemical condition or a dynamic state of interacting chemical and biological mechanisms rather than a single cause.

Effects of methadone hydrochloride on the growth of organotypic cerebellar cultures prepared from methadone-tolerant and control rats.

Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after delivery. The newly born pups were divided into two groups. One group was tested for in vivo methadone tolerance, while the animals in the othergroup were used to prepare organotypic cerebellar cultures. Various amounts of dl-methadone were added to the media of half of these cerebellum cultures. The effect of the drug in the medium was assessed by measuring explant outgrowth. Similar experiments were carried out with control animals. Statistical analysis of the data obtained in the in vivo portion of the experiment indicates that the pups of methadone-treated mothers tolerate methadone better than those of untreated mothers. The culture experiments revealed that the addition of methadone to the medium reduced explant outgrowth size and this was a dose-related effect. Also, there was significantly less outgrowth from explants prepared using pups of methadone-treated mothers as compared to the controls. There was no significant difference in the effect of methadone on the growth of cultures prepared from the methadone-tolerant and control animals.

Acid-beta-glycerophosphatase reaction products in the central nervous system mitochondria following x-ray irradiation.

A survey of the literature to date on the enzyme histochemistry of intracellular organelles has not yielded any reference to the presence of acid phosphatase reaction products in the mammalian mitochondria of the central nervous system. A combination of Gomori's acid phosphatase mehtod, however, with standard electron microscopy has disclosed the presence of enzyme reaction products in the mitochondria of the central nervous system of rats from 2 hr to 22 weeks after x-ray irradiation, as well as in a cerebral biopsy performed on a patient affected by Huntington's chorea. No enzyme reaction products, on the other hand, were observed in serial sections that had been incubated in substrates either containing sodium fluoride or lacking in beta-glycerophosphate. The abnormal mitochondrial enzyme reaction (chemical lesion) is considered to be the consequenco of the pathologic process affecting the ultrastructural-chemical organization of the organelle.