Chemical mutagenesis the Chinese hamster bone marrow as an in vivo test system

Summary

• 1. Chinese hamster fibroblast cell cultures were exposed to the alkylating mutagen, Trenimon, for 8 and 24 hrs; human fibroblast and lymphocyte cultures for 24 hrs. The dose range tested in each experiment comprised the entire span from concentrations causing aberration frequencies close to control levels up to those causing mitotic inhibition.

• 2. In all test systems a clear dose-response relationship was observed. The curves for different degrees of chromosome damage (1–2 aberrations; multiple aberrations; pulverized chromosomes) showed a similar pattern in all systems.

• 3. In Chinese hamster fibroblasts a 24 hrs exposure proved to be much more effective than an 8 hrs exposure: for a level of 50% damaged cells the drug concentration had to be increased 60-fold in the 8 hrs test. Practically no pulverized metaphases were produced in the 8 hrs experiment whereas over 70% pulverized mitoses appear after a 24 hrs exposure to the highest tolerable concentrations.

• 4. Major differences in the sensitivities of the three different test materials were found. The Chinese hamster fibroblasts proved to be most susceptible, but also showed the highest rate of spontaneous chromosome breakage. Human lymphocytes were the least sensitive. The differences found in drug sensitivity at the 50% damage level were about 15-fold between Chinese hamster and human fibroblasts and 70-fold between human fibroblasts and human lymphocytes.

• 5. Compared to the in vivo bone marrow system which responds to a very narrow dose range only (16x), the 24 hrs fibroblast system responded with a complete pattern of dose-response curves within a 32,000-fold difference between the highest and lowest test concentrations.