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.