RESUMEN
The validity and applicability of the statistical procedure - similarity pattern analysis (SPAN) - to the study of mutational distributions (MDs) was demonstrated with two sets of data. The first was mutational spectra (MS) for 697 GC to AT transitions produced with eight alkylating agents (AAs) in the lacI gene of Escherichia coli. The second was a recently summarized data on the distributions of 11562 spontaneous, radiation- and chemical-induced forward mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. They were analyzed as large two-way contingency tables (CTs) where two kinds of profiles were compared: site (or genotypic class) profiles and origin (or mutagen) profiles. To measure similarity (homogeneity) between any pair of profiles, the relevant sufficient statistics, Kastenbaum-Hirotsu squared distance (KHi(2)), was used. Collapsing the similar profiles into distinct internally homogeneous clusters named 'collapsets' revealed their similarity pattern. To facilitate the procedure, the computer program, COLLAPSE, was elaborated. The results of SPAN for the lacI spectra were found comparable with the results of their previous analysis with two multivariate statistical methods, the factor and cluster analyses. In the ad-3 data set, five collapsets were revealed among origin profiles (OPs): (I) ENU = 4NQO = 4HAQO = FANFT = SQ18506; (II) AF-2 = EI = MMS = DEP; (III) ETO = UV; (IV) AHA = PROCARB; and (V) He ions = protons. Moreover, the previous observation that MDs are dose-dependent was confirmed for X-ray-induced MDs. Profiles induced with the low doses of X-rays are similar to that induced with 85Sr, and profiles induced with the medium X-ray doses to those induced with protons and He ions. Evaluated similarities appear to be rather reasonable: mutagens with similar mode of action induce similar MDs. Similarity pattern revealed among genotypic class profiles (GCPs) seems to be also interpretable. When supplemented with descriptive cluster analysis, SPAN appears to be a fruitful methodology in MS analysis.
Asunto(s)
Operón Lac/genética , Mutágenos/farmacología , Mutación/genética , Mapeo Cromosómico , Biología Computacional/métodos , Análisis Mutacional de ADN/métodos , Análisis Mutacional de ADN/estadística & datos numéricos , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Bases de Datos Factuales/estadística & datos numéricos , Escherichia coli/genética , Mutagénesis/efectos de los fármacos , Mutagénesis/genética , Mutación/efectos de los fármacos , Mutación Puntual/efectos de los fármacos , Mutación Puntual/genética , Eliminación de Secuencia/efectos de los fármacos , Eliminación de Secuencia/genética , Rayos XRESUMEN
In contrast to 8-MOP photoaddition on DNA, the renaturation capacity of heat or alkali denatured DNA treated with 3-CPs is absent. This shows that DNA interstrand cross-links are not produced by 3-CPs photoaddition even by a dose which leads to 10(-5) survivors. At equimolar concentrations of 3-CPs or 8-MOP (5 x 10(-4) M) and a dose of 10 kJ.m-2 of 365 nm radiation, 1 molecule of 3-CPs for 4 x 10(3) nucleotides and 1 molecules of 8-MOP for 9 x 10(3) nucleotides are fixed in vivo. Since wild type cells are about 4 times more sensitive to 8-MOP than to 3-CPs photoaddition, it implies that cross-links are important in genotoxicity and that monoadditions are more easily repaired than cross-links.