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.

Chromosome examinations after medically administered lysergic acid diethylamide and dextroamphetamine.

The results of the present study demonstrate once again that, on the average, the addition of LSD in vitro leads to chromosome damage in excess of that observed in cultures without such added LSD even though nearly all of the in vitro experiments were carried out on blood cultures derived from patients who had already been started on the drug regime in vivo. By contrast, the present data provide no evidence for a measurable detrimental effect of LSD and DA when administered to patients under medical supervision. It is conceivable that an effect might have emerged had we been able to monitor chromosomes separately before and after administration of LSD and before and after administation of DA, but we consider it unlikely that either drug would exert protective action against potentially damaging consequences of the other. It is conceivable also that damaged cells are sequestered to give rise eventually to neoplasia-prone clones. The likelihood of that possibility can be determined only by long-term follow-up studies.