Carcinogenesis Induced by UV and Ionizing Radiation

The increase in the incidence of cancers in the general population, in particular the rapid increase of certain types of skin cancers in recent years , represents an alarming threat for human health and a permanent challenge for scientists. In fact, a doubling of the frequence of melanoma during the last fifteen years and a doubling of non melanoma skin cancers have been observed in the last ten years in France; already in the He of France one counts approximately 8000 new cases per year (Dore et al. 1990, Cesarini , personal communicat ion). The worldwide reported rapid rise in the incidence of these cutaneous malignancies (Glass and Hoover 1989) is almost entirely attributed to increased cutaneous exposure to solar UV radiation mostly related to present social behaviours including skin tanning and increased outdoor leisure activities (Mukhtar and Elmets 1996). Increased UV exposure due to stratospheric ozone depletion has also become a factor of concern (Henriksen et al. 1990) as well as indoor sunbed exposures (Autieret al. 1994. 1995). A 10% depletion in the total-column of ozone is expected to cause , if sustained over several decades , a 2 0 % increase in basa celt carcinoma and an about 4 0 % increase in squamous cell carcinoma (Van der Leun, 1995). However , at the present time the decrease in ozone layers observed cannot be taken as the main factor for the increase in skin cancer. The recent development of molecular biology has helped to get a better understanding of the mechanisms involved and to enlarge the classical concept of carcinogenesis including as principal steps the initiation and promotion of somatic cells. Actually, carcinogenesis is a multistep phenomenon (Figure 1). ln particular, one of the presently favoured hypotheses describes cancer induction as a consequence of the induction of somatic mutations following the induction of DNA damage , error prone or incomplete enzymatic repair of the lesions induced leading to altered gene expression , i.e. the inactivation of certain tumour suppressor genes and/or the activation of oncogenes which favour the progression of transformed cells and tumor development. Indeed, it is thought that the activation of genes which control cell proliferation facilitates the expansion and clonal selection of initiated and genetically instable cells showing an acceleration in cell cycle progression. If such cells escape the immunologic survey system, tumor cells may built foci and, depending on their nature (see models for the induction of melanoma (Albino and Fountain 1996) and squamous cell carcinoma (Ziegler et al. 1996)), may start spreading over the whole body in form of metastasis. That the individual repair capacities play an important role in carcinogenesis has become evident from studies on human cancer-prone diseases such as Xeroderma pigmentosum (XP) (Sarasin 1994, Kraemer 1996, Grossman and Wei 1995), Fanconi ' s Anemia (FA) (Moustacchi 1994) and Ataxia telangectasia (AT) (Aurias 1994). For example , X P patients are more than 1000 fold more susceptible to the induction of skin cancers by sunlight than normal individuals (Kraemer 1996). Ultraviolet radiation can be distinguished from low density ionizing radiation such as X-rays by differences in efficacy and specificity of the cancer induced. It appears that at comparable cytotoxic level ultraviolet radiation exerts a higher mutagenic and carcinogenic potential than ionizing radiation. This is probably due to differences in energy deposition in cellular targets and in the frequency and type of lesions induced by these agents . In physics and many industrial and medical applications, lasers are employed emitting strong monochromatic light in different regions of the electromagnetic spectrum including ultraviolet, visible and infrared radiation as well as soft X-rays and very short wave ultraviolet radiation < 200 nm . Despite the fact that these highenergy monochromatic light sources are highly