The inhibitory effect of tetracycline on osteogenesis in organ culture.

Two characteristics of the tetracycline-group antibiotics have recently focused the special attention of teratologists: these drugs are known to pass readily across the placental'barrier' (Charles, 1954; Frost & Villanueva, 1960; Gibbons & Reichelderfer, 1960; Hughes, Lee & Flood, 1965; Simpson, Burnette & Bawden, 1967), and they are incorporated into the foetal skeleton, where they may remain for long periods and can be detected owing to their brilliant fluorescence (Rail, Loo, Lane & Kelly, 1957; Milch, Rail & Tobie, 1957, 1958; Bevelander, Rolle & Cohlan, 1961; Urist & Ibsen, 1963; Michelson, 1964). The question of whether they exert a harmful effect on bone formation and mineralization in mammals, however, is still a matter of controversy. There is no doubt that tetracycline interferes with mineralization of the skeletal tissue in certain lower vertebrates (Bevelander, Goldberg & Nakahara, 1960; Bevelander & Cohlan, 1962), and prevents calcification of mammalian bones in organ culture (Saxen, 1966«, b). Reports of in vivo studies in mammalian species have yielded more confusing results. In 1957, Filippi & Mela reported minor skeletal malformations in mouse foetuses after maternal tetracycline administration, and later Cohlan, Bevelander & Tiamsic (1963) observed depression of the growth rate of the long bones of premature children receiving high doses of tetracycline. Correspondingly, a reduction of the foetal weight has been reported to result from administration of tetracycline to the mother (Bevelander & Cohlan, 1962; Cohlan et al. 1963). On the other hand, neither experiments on rats nor observations on children have confirmed all these reports, as Oxytetracycline appears to have no adverse effects on mineralization (Chu, O'Hara & Keitel, 1963; Likins & Pakis, 1965). In addition to differences in the dose and mode of administration, these conflicting results may also be due to differences between the various members of the