Distribution of marker-Y chromosome containing cells in different tissues of a Turner mosaic patient with mixed gonadal dysgenesis.

We here describe a 12-year-old girl with numerous Turner stigmata and virilized external genitalia. Chromosome analysis of PHA stimulated lymphocytes using different banding techniques revealed a 45,X/46,X,+mar Turner mosaicism with the prominent marker present in about 90% of the blood cells. A PCR-based analysis using a set of 9 STS from different regions of the human Y chromosome indicated the presence of Y chromosomal material with a deletion breakpoint most likely within deletion interval 6.

Cytogenetic effects of phorbol ester tumor promoters: possible role in multistep tumorigenesis.

The conversion step of multistage tumorigenesis in mouse skin effected by TPA (12-O-tetradecanoylphorbol-13-acetate) but not by RPA (12-O-retinoylphorbol-13-acetate) may be best explained by the clastogenic (and mitogenic) activity of TPA. In mouse keratinocytes in vitro as well as in vivo TPA (but not RPA) was shown earlier to induce a significant degree of chromosomal aberrations. Details of the clastogenic action of TPA were studied in HeLa cells.

Cytogenetic effects caused by phorbol ester tumor promoters in HeLa cells: mechanistic aspects.

The effect of the convertogenic ('first-stage') tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) and the non-convertogenic ('second-stage') tumor promoter RPA (12-O-retinoylphorbol-13-acetate) on chromosomes was investigated in HeLa cells which have previously been shown to exhibit a radiomimetic response to TPA. As in the case of mouse keratinocytes, only TPA had a significant clastogenic activity at non-cytotoxic concentrations ranging from 10(-8) to 10(-6) M measured after 24 and 48 h. The values observed with RPA did not differ significantly from values observed in the presence of the solvent (acetone, 0.

Tumor induction in initiated mouse skin by phorbol esters and methyl methanesulfonate: correlation between chromosomal damage and conversion ('stage I of tumor promotion') in vivo.

Using the multistage (initiation-conversion-promotion) protocol we have studied the effects of methyl methanesulfonate (MMS), a well-known alkylating and clastogenic agent, on tumor development in NMRI mouse skin in vivo. When topically applied in a dose up to 400 mumol MMS did not exhibit any initiating efficacy while under identical conditions chromosomal damage (mainly breaks and gaps) was induced in epidermis. A dose of 100 mumol MMS was found to be almost as clastogenic as 10 nmol of the convertogenic tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), whereas the non-convertogenic promoter 12-O-retinoylphorbol-13-acetate (RPA, 10 nmol) did not induce chromosomal aberrations in vivo.

Cytogenetic effects caused by phorbol ester tumor promoters in primary mouse keratinocyte cultures: correlation with the convertogenic activity of TPA in multistage skin carcinogenesis.

The effects of the convertogenic ('first-stage') tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the non-convertogenic ('second stage') tumor promoter 12-O-retinoyl-phorbol-13-acetate (RPA) and the non-promoting phorbol esters 4-O-MeTPA and 4-alpha-PDD on the chromosomes of mouse keratinocytes in primary cultures were investigated. In these target cells of tumor promotion TPA caused severe numerical and structural chromosomal aberrations, which were evident after two cell cycles and accumulated after multiple applications. Numerical aberrations were visible as hypo- and hyperdiploidy, with non-random loss or gain of specific chromosomes.