Induced mutation factor

Human data regarding reproductive/developmental effects due to lewisite exposure are inconclusive because of confounding factors such as concurrent exposure to other agents such as sulfur mustards and incomplete exposure data. Yamakido et al. (1985) studied workers from the Okuno-jima (Japan) factory where mustard and lewisite were manufactured in the World War II era, and noted no evidence of agent-induced mutations. 

While only a simulation, this model still serves to illustrate 1) the potential impact of cytotoxicity upon the dynamics of DNA turnover and the background rate of spontaneous mutation/proto-oncogene activation or, in the case of genotoxins, the rate of chemically-induced mutation and 2) the potentially large differences in potency, at a macromolecular level, which may exist between these two classes of carcinogens. One factor which this model does not take into account, however, is the potential Impact of purely receptor-mediated promotional activity of a cytotoxic compound. 

Transcription stimulates excision repair both in E. coli (Mellon and Hanawalt, 1989) and in humans (Bohr et al., 1985 Mellon et at, 1987) in a process dependent on proteins called transcription-repair coupling factors (TRCFs). In E. coli the mfd gene encodes the TRCF (Selby and Sancar, 1991,1993 Selby etaZ., 1991), and cells mutated in this gene exhibit modest UV sensitivity but a disproportionately increased rate of UV-induced mutations and lack of mutation frequency decline (mfd) on holding in minimal medium after irradiation and before plating (Witkin, 1994). 

Many mutagenic compounds are very labile under the treatment conditions used for the Neurospora conidia. Sometimes mutagens are used in such minute concentrations that the conidia will absorb a considerable amount of the compound from the solution e.g., 2 X 10 conidia will absorb 2.5 X 10" M ICR-170 (an acridine mustard derivative). These factors must be considered when the kinetics of the induced mutation frequency is measured as a function of increasing time. The mutation-induction curves... 

There are other factors that may affect the mutation frequency. We have already shown that the cell density, time of addition of selective agent (mutation expression), and concentration of selective agents can modify the final number of induced mutations. The following two situations may further decrease or increase the number of detectable mutations ... 

Ultraviolet, x-rays and ionizing radiations readily break DNA chains and in this way can induce mutations. In general, mutations can be induced by chemical attack and by accidental factors as well as by radiation. 

Mutagen Cell type Locus studied Induced mutation rate Spontaneous mutation rate Induced rate factor Reference... 

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