Re: In7: Very interesting paper on CTD and SCC.

From: Frank de Gruijl; M.Huisman@DIGD.AZU.NL
Date: 12/7/97
Time: 12:28:27 PM
Remote Name:


Hi Diane, thanks for your careful comments, which I will try to answer point by point before tending the garden: a) we discussed the p53-as at earlier occassions, but I have to admit that I still do not know much about it: the papers on the mitotic-check point (not really a G2 arrest) function of p53 do not refer to the 'as' form, but I should perhaps look at this more closely. b) I have no particular reference at hand for the fact that CTD do not appear to be mutagenic: a good example of this is of course the complete lack of UV-induced p53 mutations at orginal TT sites in the skin tumor from hairless mice as discussed in our paper. But the same lack of mutations at TT has been observed in other assays. c) I doubt whether apoptosis formation would be a good indicator of SCC risk because daily dosis well below the sunburn level are adequate for inducing SCC. This probably explains why we have not seen a faster development of UV-induced SCC in heterozygous (+/-) p53 k.o. mice at low daily doses, whereas we do see at high daily doses (in prep.). d) a good early indicator of UVA1-related SCC risk is still the 'Scarlet Pimpernel', but very important to identify. e) the relationship between sunburn and SCC goes back to point c: Sunburn or sunburn cells do not appear to be a prerequisite for tumor formation. f) we have examined skin samples from a group with 1/2 MED daily doses of UVA1 (in connection with a late induction of itching), and as far as I can remember, did not observe any gross induction of sunburn cells in the epidermis; the same goes for the low dose UVB groups, but we probably have to look at this more closely. In fact, we are involved in experiments looking at UV-apoptosis and tumor induction in various DNA repair deficient mouse strains. g) my aim ultimately is indeed to come up with equations that predictively link measures of DNA damage (incl. mutations) to tumor risk. I think that a better identification of the important target cells and target genes (and perhaps epigenetic targets) are essential here. h) the double discrimination was so much a software but more a hardware problem: the machine did measure the full pulse attributes (i.e. no pulse length or area under the curve).

Back to the list of comments