Antipain inhibits N-methyl-N'-nitro-N-nitrosoguanidine-induced transformation and increases chromosomal aberrations.

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Abstract
The morphologic transformation induced in Syrian hamster embryo cells by [the carcinogen] N-methyl-N''-nitro-N-nitrosoguanidine (MNNG) (0.25 .mu.g/ml of medium) is inhibited by posttreatment with antipain (6-600 .mu.g/ml), a protease inhibitor, but is unaffected by pretreatment. DNA replication relative to untreated controls is not affected by MNNG, antipain or the combination of the 2; no synergistic lethality of antipain and MNNG occurred, as reflected in the cloning efficiency. Antipain was ineffective in influencing MNNG-induced sister chromatid exchanges but increased frequencies of chromosomal aberration (per metaphase) at 10, 26 and 40 h when cells were treated with MNNG followed by antipain 10 min later, the procedure used in the transformation studies. Antipain also increased the average number of aberrations at the 2nd mitosis (34 h) when the MNNG concentration was doubled. Chromatid exchanges increased 26 h posttreatment with the combination of MNNG and antipain used for transformation. No difference in MNNG-induced aberrations was observed when antipain preceded MNNG by 24 h. Although the mode of action of antipain is unknown, antipain does not inhibit transformation by suppressing chromosomal rearrangements that could convert recessive mutations to the homozygous state.