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Problems of extrapolation from experimental data to human mutagenesis
278 pentachlorophenol (at 250 /~g/plate with $9 and 25 /~g/plate without $9) and tecnazene (at 75 # g / p l a t e with $9 and at 250 /~g/plate without $9) were toxic to Salmonella, so that no reliable results at these or higher doses could be obtained. Diaminobenzidine is mutagenic with metabolic activation on TA98 and TA 1538 and without $9 on TA1537, TA1535 and TA1538.
92 Lyon, M.F., M.R.C. Radiobiology Unit, Harwell, Oxon O X l l 0 R D (Great Britain)
Problems of extrapolation from experimental data to human mutagenesis Extrapolation from experimental data to genetic hazards in man involves extrapolation concerning dose, cell type, species, and from mutation rates to disease incidence. Dose can be measured at various sites from the exposure dose in the environment to the molecular dose in DNA. Transitions from one site to another and from D N A dose to mutational effect may be non-linear. Thus dose should be measured as near the molecular level as possible, and extrapolations should be made from experimental doses nearest to environmental. At present one cannot extrapolate quantitatively from somatic cells to germ cells. Thus, only germ-cell data, from the most relevant stage, and from the species nearest to man should be used. In order to estimate increases in incidence of genetic disease resulting from a given increase in mutation rate the method proposed is to prepare a table of cases of disease resulting from a given proportional rise in mutation rate, and then to express the mutation rate in such a way that the table can be consulted.
93 L~ihdetie, J., Institute of Biomedicine, Department of Anatomy, University of Turku, SF-20520 Turku 52 (Finland)
Mieronuclei induced by adriamycin in male meiotic prophase A new method to study male germ-cell mutagenesis analogous to the bone-marrow micronucleus test has been used to analyze chromosome damage induced by X-rays (L~hdetie, J. and Parvinen, M., Mutation Res., 81 (1981) 103-115). We are currently studying some chemical model mutagens in order to develop and evaluate this meiotic micronucleus method. In the present study the sensitivities of 8 meiotic stages to induction of micronuclei were analyzed. Male rats were treated with a single i.p. injection of adriamycin, with doses of 5 or 10 m g / k g . Micronuclei were scored in early spermatids 1, 3,
92 Lyon, M.F., M.R.C. Radiobiology Unit, Harwell, Oxon O X l l 0 R D (Great Britain)
Problems of extrapolation from experimental data to human mutagenesis Extrapolation from experimental data to genetic hazards in man involves extrapolation concerning dose, cell type, species, and from mutation rates to disease incidence. Dose can be measured at various sites from the exposure dose in the environment to the molecular dose in DNA. Transitions from one site to another and from D N A dose to mutational effect may be non-linear. Thus dose should be measured as near the molecular level as possible, and extrapolations should be made from experimental doses nearest to environmental. At present one cannot extrapolate quantitatively from somatic cells to germ cells. Thus, only germ-cell data, from the most relevant stage, and from the species nearest to man should be used. In order to estimate increases in incidence of genetic disease resulting from a given increase in mutation rate the method proposed is to prepare a table of cases of disease resulting from a given proportional rise in mutation rate, and then to express the mutation rate in such a way that the table can be consulted.
93 L~ihdetie, J., Institute of Biomedicine, Department of Anatomy, University of Turku, SF-20520 Turku 52 (Finland)
Mieronuclei induced by adriamycin in male meiotic prophase A new method to study male germ-cell mutagenesis analogous to the bone-marrow micronucleus test has been used to analyze chromosome damage induced by X-rays (L~hdetie, J. and Parvinen, M., Mutation Res., 81 (1981) 103-115). We are currently studying some chemical model mutagens in order to develop and evaluate this meiotic micronucleus method. In the present study the sensitivities of 8 meiotic stages to induction of micronuclei were analyzed. Male rats were treated with a single i.p. injection of adriamycin, with doses of 5 or 10 m g / k g . Micronuclei were scored in early spermatids 1, 3,