The induction of dominant lethal mutations in rats and mice with triethylenemelamine (TEM)

Abstract

1. TEM resembles X-rays in inducing dominant lethal mutations in the sperm of rats and mice and sterilizing type B spermatogonia. Beyond this, however, there are several important differences.2. The relative ease with which TEM and X-rays affect sperm and spermatogonia varies greatly. The X-ray dose which produces 50% dominant lethals in sperm (500 rad) sterilizes spermatocytes and type B spermatogonia, and has such a drastic effect on type A spermatogonia that recovery of fertility is delayed for 2½ months. The TEM dose which produces the same mutation rate in sperm (0·1 mg./kg. rat) has no detectable effect on pre-meiotic stages. Even 1 mg./kg. only sterilizes the most sensitive stage, type B spermatogonia.3. Taking immature sperm as the standard, mature sperm are more sensitive to X-rays, but less sensitive to TEM, and early spermatids, the most sensitive stage to X-ray-induced dominant lethals, are highly resistant to TEM.4. Spermatocytes, in which X-rays yield a mutation rate equal to immaturesperm, are highly resistant to TEM.5. To produce the same mutation rate in immature sperm, mice require twice as much TEM as the rat in mg./kg., though approximately the same X-ray dose.6. In contrast to mid-stage rat spermatids, which are the most sensitive stage to TEM, mouse mid-stage spermatids are resistant.