1994;54:5081-5085. Cancer Res   Francesco D'Agostini and Silvio De Flora  MicePotent Carcinogenicity of Uncovered Halogen Lamps in Hairless

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ICANCER RESEARCH54, 5081-5085, October 1, 1994

ABSTRACT

Uncovered halogen quartz lamps, which are potently genotoxic both inprokaryotic and human cells due to the emission of far-UV radiation(UVB and UVC), were assayed for carcinogenicity In three strains ofhairless mice (SKH-1, MF-1, and C3H) of both sexes. As assessed In 5Independent experiments, no spontaneous skin tumor was observed, evenafter more than 2 years, in 49 animals used as unexposed controls or In 29animals exposed to halogen lamps equipped with a common glass cover. Incontrast, almost all of the 185 mice exposed to the light emitted bylow-voltage (12 V) and low-power (SO W) tungsten bulbs, equipped withdichroic diffusers, contracted multiple skin tumors of various histologicaltype, both benign and malignant Tumors were induced over a range ofilluminance levels (1,000, 3,333, 5,000, and 10,000 lux) and daily exposure

times (1.5, 3, 6, and 12 h). The tumor latency times were quite short andsignificanfly correlated with the daily exposure limes, as well as with the

square of the distance (46—194cm) from the illumination source. Acarcinogenic effect was even observed when exposure was discontinuedwellbefore the appearance of skin lesions.Both in vitrogenotoxicitydataand animal carcinogenkity data support the view that the light emitted byuncovered halogen lamps, to which an enormous number of individuals

are exposed, may pose carcinogenic risks to humans. Without renouncingthe benefits of this modern illumination system, UV-blockingdevicesshould be compulsory.

INTRODUCTION

Halogen lamps provide a modern and attractive illumination systemwhich is used more and more extensively in many countries at home,in offices, and in shops. Therefore, humans may be heavily exposedto the light emitted by this kind of lamp, often for several hours a dayand at relatively high illuminance levels, e.g., when halogen quartzbulbs are installed in desktop lamps or are incorporated into dichroicdiffusers used as multiple spotlights. We demonstrated previously thatthe light emitted by uncovered halogen lamps is potently mutagenic inhisSalmonella typhimurium strains (1) and genotoxic in Escherichiacoli strains lacking DNA repair mechanisms, especially excisionrepair and SOS repair pathways (2). A clastogenic effect was produced in vitro by halogen lamps in human cells, as shown by theincrease of micronucleus frequency in cultured peripheral blood lymphocytes (3). Moreover, the results of a small pilot study with 12hairless mice suggested that halogen quartz bulbs are inducers of skin

tumors (4). All the investigated genotoxic and carcinogenic effectscould be totally prevented by covering the quartz bulbs with commonglass sheets (1—4).

Here we report the results of extensive carcinogenicity assays,providing sound evidence for the dose- and time-related skin carcinogenicity of this illumination system, which induces multiple skintumors of various histological types in hairless mice within a shortlatency period and with a prevalence of virtually 100% among cx

Received 4/18/94; accepted 8/1/94.The costs of publication of this article were defrayed in part by the payment of page

charges. This article must therefore be hereby marked advertisement in accordance with18 U.S.C. Section 1734 solely to indicate this fact.

I This study was funded in part by the Italian Ministry for University and Scientific

Technological Research (40 and 60% grants) and by the CNR Targeted Project “Prevention and Control of Disease Factors-FATMA.―

2 To whom requests for reprints should be addressed, at Institute of Hygiene and

Preventive Medicine, University of Genoa, via Pastore 1, 1-16132Genoa, Italy.

posed animals versus 0% of unexposed controls and of animalsexposed to glass-covered lamps.

MATERIALS AND METHODS

Three strains of hairless mice, i.e., 5}CJ.I.1albino (Charles River Italia,Calco, Como, Italy), MF-1/Ola/Hsd albino, and C3HTFif-pigmented mice(both from Nossan, Correzzana, Milano, Italy) were used. Four-week-oldanimals, weighing 25—30g, were acclimatized for 10 days and randomlydivided into groups, as indicated in Table 1. They were housed 4—5/makroloncage, given mouse chow and tap water ad libitum, and maintainedunder controlled temperature (27 ±1°C)and relative humidity (50 ±5%)conditions.

Control animals were kept under natural 12 h dark/12 h light cycle (win

dow-filtered daylight). All remaining mice were exposed under the variousexperimental conditions detailed in Table 1 to the light emitted by spotlightsequipped with dichroic diffusers incorporating tungsten halogen quartz lamps(12 V, 50 W) Model M50; Thorn Lighting Ltd., United Kingdom). Each cage

was illuminated by a single spotlight. The halogen bulbs were replaced every

6 months. The mice of three experimental groups were exposed to the light of

quartz bulbs protected with a 2-mm-thick common glass cover, positioned 5

mm below the lamp in order to allow air circulation and to prevent overheating.illuminance levels, which were not modified by the glass cover, were meastired on the bottom of each cage by using an electronic luxmeter (Model1300/V; ICE, Milano, Italy).

The animals were examined daily for survival and once a week for the scoreof skin lesions. The skin tumor yield is reported both in terms of prevalence(i.e., the percentage of tumor-bearing mice among surviving animals) andmultiplicity (i.e., the mean number of tumors/mouse). Representative skinlesions of mice, either dead as a consequence of the disease or killed in anadvanced stage of development of tumors, were excised, fixed in 10% formalin, and embedded in paraffin, and then tissue sections were stained withhematoxylin and eosin. The histological type of tumors was defined accordingto the classification proposed by Gallagher et a!. (5).

The comparison of survival curves for the different experimental groupswas made by x2 analysis on data recorded every 5 weeks. Correlation (r)coefficients and their statistical significance were calculated for evaluating the

relationships between tumor formation and (a) dose of absorbed light (illuminance), which varied depending on the distance from the halogen lamp, (b)daily exposure time, and (c) duration of exposure.

Animal care was in accord with our national guidelines, and mice did not

receive any treatment other than exposure to the illumination system understudy.

RESULTS

Table 1 summarizes the results of five independent experimentsinvolving the use of a total of 243 hairless mice of 3 strains (SKH-1,MF-1, and C3H), both males and females, exposed to various lightintensity and time conditions. The minimum, median, and maximumlatency periods, corresponding within each group to the lag timesneeded for the macroscopical appearance of tumors in the earliestanimal, in 50% of the animals and in the last animal, respectively, arealso reported.

No spontaneous skin tumor could be observed in our experiments,as shown by the absolute lack of lesions in the 49 mice used ascontrols (4 SKH-1, 40 MF-1, and 5 C3H) and in the 29 mice exposedto glass-covered halogen lamps (4 5KB-i, 20 MF-1, and 5 C3H),even after observation for more than 2 years since the start of theexperiments.

5081

Potent Carcinogenicity of Uncovered Halogen Lamps in Hairless Mice'

Francesco D'Agostini and Silvio De Flora2

Instituteof Hygieneand PreventiveMedicine.Universityof Genoa.1-16132Genoa,Italy

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Table 1Outline of thecarcinogenicitv experimentsperformedwith halogen lamps in hairlessmiceExperimentStrainMice

SexNo.Exposure

conditionsSkin tumorsLatencyperiod(weeks)Illuminance

(lux)GlassCycle

cover (h/day)Time(weeks)Prevalence

Multiplicity(% of tumor- (mean no. ofbearing mice)tumors/mice)MinimumMedianMaximumISKH-lF

j@I;@

.@ :@:.,

@1@@ ,4,@t;@P:;i,:@ 1@t\‘LR I @‘‘:@@@ \\I1H(()

CARCINOGENICITYOF HALOGEN LAMPS

4 a4 10,0004 10,000

2 SKH-l F 5 10,0005 10,0005 10,0005 10,000

3 SKH-l F 5 10,0005 10,0005 10,0005 10,0005 10,000

4 MF-I M 20 —20 10,000

MF-l F 20 —20 10,00040 10,00020 3,33320 1,000

5 C3H F 5 -5 10,0008 10,0008 5,000

0Yes 12 122 0No 12 36 100

No 12 35 100No 6 52 100No 3 63 100No 1.5 63 100

No 12 16 100No 12 20 100No 12 24 100No 12 28 100No 12 40 100

0No 12 39 100

0Yes 12 121 0No 12 52 100No 12 102 100No 12 121 66.7

0Yes 12 58 0No 12 46 100No 12 58 100

0 >1220 >122

18.5 16

20.2 2015.0 2811.0 403.4 52

8.2 2514.2 2315.4 2220.4 2421.0 21

0 >12115.6 230 >1210 >121

11.8 2310.9 581.3 101

0 >580 >586.4 29

10.0 41

21 24

23 2639 4145 5858 66

30 3526 3827 3428 3125 31

29 34

29 5175 93

107 >121

34 4445 50

a Dashes indicate non-exposure to halogen lamps.

In contrast, almost all of the 185 mice exposed to tungsten

halogen lamps at illuminance levels ranging between 1,000 and10,000 lux, for daily cycles ranging between 1.5 and 12 h, and forperiods ranging between 16 and 121 weeks, contracted multiple

skin tumors. Fig. 1 shows at a glance the striking difference in the

appearance of SKH-l mice exposed to the light of either uncoveredor covered halogen quartz bulbs. In general, the skin lesions wereinitially detected either as erythematous areas or directly as papulae and noduli, which in some cases tended to become eroded andulcerated. The tumors increased both in number and size with timeand often became confluent, thereby hampering an accurate enumeration in late stages. Skin tumors of large size (up to 4.1 cm in

diameter and 10.2 g in weight) were recorded in several cases. A

few regressions of lesions were noted. Fig. 2 shows an example@@time-related evolution of skin lesions in a MF-1 mouse exposed@an uncovered halogen lamp.

As evaluated by x@analysis on data recorded every 5@@@ L@@ i@@was no statistically significant difference in survival between@@@@@@@@@mice and mice exposed to 10,000 lux with glass covers, or to@ I i@@

ered lamps at illuminance levels of 5,000, 3,333, or 1,000 lux. I )@ i@@@the massive occurrence of skin tumors, survival was@ i@@ i@@ tI@@@ I@@@decreased only in groups of mice exposed to 10,000 lux@@@@@@@@ \@@@@lamps) for 12 h/day. Interim killings were also performed@@ i@@@groups for histological analyses.

The histological nature of skin lesions in the three mouse@@ i@ i@ i@was evaluated in experiments 1, 4, and 5. Some@@ i@@@@@@

P.@@

@j.,.

•“I:@@@@ •

.. .

@ \ \V I T 1@1C)@ T C C)

r

\@ I@ R

Fig. 1. Appearance of skin lesions induced by uncovered halogen tungsten lamps in female SKH-1 hairless mice after 8 months of exposure, 12 h/day, to the light bydichroic lamp incorporating a 12 V. 50 W halogen quartz bulb, either uncovered (left) or covered (right) with a glass sheet (see Table 1; experiment 1).

5082

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CARC1NOGENK@@@YOF HALOGEN lAMPS

WEEK 29 \\kNK @1

I@1

\\‘FiFIK:@@@@ \\[1@K @5 \\‘[IIK@Fig. 2. Time-related evolution of skin lesions in a MF-1 hairless mouse exposed 12 h/day to the light emitted by an uncovered dichroic lamp incorporating a 12 V, 50 W halogen

quartz bulb.

recorded among SKH-1 (38 lesions analyzed after 36 weeks of exposure), MF-1 (110 lesions after 40 weeks), and C3H mice (42 lesionsafter 58 weeks). In particular, in these three mouse strains we observed epidermal hyperplasias (21.1, 31.9, and 38.1%), papillomas(3L6, 12.0, and 19.0%), actinic keratosis (2.6, 6.1, and 7.1%), keratoacanthoma-like tumors (5.3, 4.7, and 4.7%), appendage-basal tumors (10.5, 8.1, and 16.6%), carcinomas in situ (5.3, 24.1, and 7.1%),and squamocellular carcinomas (23.7, 12.9, and 7.1%), respectively.Furthermore, a few areas of atypical melanocyte proliferation werealso observed in C3H mice.

A 100% prevalence of tumorswas observed in all groups of mice(totaling 69 animals) exposed to uncovered halogen lamps for 12h/day at an illuminance level of 10,000 lux. The rank of sensitivity ofthe three mouse strains was SKH-1 > MF-1 > C3H, as shown bymultiplicity values of 18.5 (experiment 1), 20.2 (experiment 2), and

21.0 (experiment 3) tumors/mouse in female SKH-1 mice; of 15.6(males) and 11.8 (females) tumors/mouse in MF-1 mice (experiment4); and of 6.4 tumors/mouse in female C3H mice (experiment 5).Moreover, the latency period was shorter in SKH-1 mice (medianvalues of 21, 23, and 25 weeks; experiments 1, 2, and 3, respectively)than in MF-1 mice (29 weeks in both males and females; experiment4) and in C3H mice (45 weeks; experiment 5).

The dose dependence was investigated in MF-1 (experiment 4) andOH (experiment 5) mice. Fig. 3 reports in detail the time course oftumor yield in female MF-1 mice exposed for 12 h/day to threedifferent levels of intensity of illuminance, i.e., 10,000, 3,333, and1,000 lux. These illuminance levels were obtained by positioning the

halogen lamps at distances of 46, 102, and 194 cm, respectively, from

the bottom of cages. It is evident, as also indicated in Table 1, that thelatency tumor-induction time tended to increase by lowering theilluminance levels. Moreover, after appearance of the earliest lesions,the growth of both tumor multiplicity and prevalence was slower inthe low-exposure groups. Some fluctuations in the curves represented

5083

14 Overlapping ‘@ ,@ Overlapping12 lesions I o 10,000lux 1 lesions

@@ 3333lux@10

8

2

C.,

0@

C.,Ca,

>

0@60 100 120

Time (weeks)Fig. 3. Time-related evolution of skin tumor yield in MF-1 female halrlcss mice

exposed 12 h/day to the light emitted by an uncovered dichroic lamp incorporating a 12V, 50 W halogen quartz bulb, at three different illuminance levels (10,000, 3,333, and1,000 lux). See Table 1 for details (experiment 4).

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CARCINOGENICITYOF HALOGEN LAMPS

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5084

DISCUSSION

The results of the present study provide sound evidence that uncovered halogen lamps are potently carcinogenic in hairless mice byinducing skin tumors with a quite short latency period, a prevalence ofvirtually 100%, and a high multiplicity. As it will be described inmore detail in a separate article3 in which the immunohistochemicaldetection of p53 protein in halogen-induced skin tumors will be alsoreported, the histological analysis revealed the presence of a variety ofmicroscopic lesions, both benign and malignant. Compared to the

results generated in animal studies with chemical carcinogens, gen

erally requiring doses which are orders of magnitude higher than thoseexpected following human exposure, it should be emphasized that thecarcinogenic effect was also produced by moderate exposures to thelight sources. Even if we refrain from extrapolating down the regression lines reported in Fig. 4 because we do not know whether these

lines may still be linear at exposure times or doses lower than thosetested, it is meaningful that skin tumors could be induced followingmoderate daily exposures (1 .5 h) or moderate illuminance levels(1,000 lux), accounted for by a 50-W spotlight placed at about 2 m ofdistance, i.e., under exposure conditions which are frequent in humans. It is also noteworthy that tumors were even induced whenexposure to halogen lamps was discontinued well before the macroscopical appearance of skin lesions. However, the multiplicity oftumors was inversely related to the period of exposure. These data arein agreement with findings concerning the development of skin tumors induced by chemicals in mice, supporting the view that themalignant conversion stage of tumor progression occurs spontaneously (6) but may be enhanced by treatment of animals with genotoxicagents (7). A decrease in the multiplicity of skin tumors was alsoobserved by discontinuing exposure of hairless mice to UV radiationin the 280—370nm range, but in this case the induction time wasincreased proportionally (8).

The comparative carcinogenesis action spectra in humans and hairless mice, which have been used for 30 years as an experimentalmodel for photocarcinogenesis, are not known. Nevertheless, it isnoteworthy that acute responses to UV radiation, such as edema, werefound to be very similar in albino SKH-1 hairless mice and humans(9). The responsibility of UV radiation in inducing skin tumors inhumans and animal models is well established (10), and carcinogenicity patterns have been investigated in hairless mice with radiationof different wavelengths, i.e., UVA (315—380nm; Ref. 11), UVB(280—315nm; Ref. 12), and UVC (100—280nm; Ref. 13). Uncoveredtungsten halogen lamps do emit UV light due to the permeability oftheir quartz bulb to this kind of radiation, and the emission covers awavelength spectrum starting from the UVC region (14). The involve

ment of far-UV wavelengths in the genotoxicity of halogen lamps iswell supported by our experiments in S. zyphimurium, in which thelight was filtered through either color filters, cutting off certainspectral regions, or UV interference filters, selectively allowing transmittance of UVA, UVB, or UVC radiation. While the mutagenicity ofsunlight was distributed over a wide UV spectrum and the mutagenicity of fluorescent lamps was mainly due to UVB, the mutagenicity

of halogen lamps depended on UVB and UVC emissions (1). Moreover, the spectrum of sensitivity of E. coli strains lacking a variety ofDNA repair mechanisms was quite similar by using halogen lampsand a monochromatic UVC source (2). It is noteworthy that atequivalent radiant energy the mutagenic potency of a 254-nm UVCsource was 8400-fold higher than that of a 365-nm UVA source (1).

3 F. D'Agostini, P. Fiallo, C. Di Marco, and S. Dc Flora, Detection of p53 andhistopathological classification ofskin tumors induced by halogen lamps in hairless mice,manuscript in preparation.

0 Minimum

L@ Median

0 Maximum

20 40 60 80 100 120

Latency period (weeks)Fig. 4. Latency periods needed for the formation of skin tumors induced by the light

emitted by an uncovered dichroic lamp incorporating a 12 V, 50 W halogen quartz bulb,as related either to the square of the distance from the halogen lamp in MF-1 mice exposed12 h/day (Lower Panel) (see Table 1; experiment 4) or to the daily exposure times inSKH-l hairless mice exposed to 10,000 lux (Upper Panel) (see Table 1; experiment 2).

in Fig. 3 depended on contingent factors, such as regression of some

lesions, interim deaths of animals bearing multiple tumors, or conflu

ence of enlarging lesions. As shown in Fig. 4 (lower panel), theminimum, median, and maximum latency periods were inverselyrelated to the square of the distance from the illumination source, withhigh and significant correlation indices between the two parameters(r 0.99, and 1.00 for minimum and median latency periods, respectively; both P < 0.01). An evident dose-related effect was also observed in C3H mice exposed to 10,000 lux (distance of 46 cm) and

5,000 lux (79 cm) (Table 1; experiment 5).

The time dependence was explored by varying the duration of thedaily exposure, i.e., 12, 6, 3, and 1.5 h/day, at an equivalent illuminance level (10,000 lux) (Table 1; experiment 2). Both prevalence andmultiplicity of skin tumors decreased by shortening the exposure

times, and the curves indicating the development of lesions tended to

become less steep (Fig. 5). Nevertheless, it is noteworthy that even inthe group exposed for only 1.5 h/day, the majority of animals developed skin lesions. By drawing the regression lines between the latencyperiods and the daily exposure times, a linear correlation was pointedout (Fig. 4, upper panel), and the correlation indices (r = 1.0 for theminimum latency period; r = 0.99 for the median and maximumvalues) were highly significant (P < 0.01).

In another experiment (Table 1; experiment 3), exposure of SKH-1female mice to halogen lamps (10,000 lux; 12 h/day), was eithercontinued until the end of the experiment (40 weeks) or discontinuedafter 16, 20, 24, or 28 weeks. All mice in these 5 groups developedskin tumors, and the latency periods were just marginally increased by

stopping exposure to the carcinogenic agent. Interestingly enough, inthe first two groups the lesions appeared a few weeks after stoppingthe exposure. The five groups differed in the multiplicity of tumors,which was inversely related to the exposure period to halogen lamps

(r 0.88, P < 0.05). Moreover, as estimated from our experience onthe histological classification of lesions as related to their macroscopical appearance, the proportion of malignant tumors was lower whenexposure was stopped earlier, i.e., roughly 31% of lesions weremalignant when exposure was discontinued after 16 weeks, 46% after20 weeks, 49% after 24 weeks, 51% after 28 weeks, and 55% whenexposure was continued until the end of the experiment.

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CARCINOGENICITYOF HALOGEN LAMPS

22

20

1816

>@ 14

.2 120.

@ 10

6

This implies that the emission of even small amounts of UVCradiation from an illumination system is expected to producebiological effects, which apparently were thus far overlooked inthe case of halogen lamps. Far-UV radiation is likely to be therange of wavelength inducing melanoma (15).

The bacterial genotoxicity of uncovered halogen lamps is remarkably higher, even at considerably lower illuminance levels, than thatof sunlight (1, 2), which is well known to contribute to cancerprevalence and mortality in humans (10). The genotoxicity of halogenlamps is also much higher than that of fluorescent lamps, whosecarcinogenicity is under debate (16). Even in the absence of direct

evidence in humans, which would be extremely difficult to achieve inan epidemiological study, the outcome of the carcinogenicity assaysreported here, together with the documented genotoxicity, not only inrepair-deficient bacteria (1, 2) but also in normal human cells (3),leaves little doubt that halogen lamps may be potentially carcinogenicin humans. Skin cancer risk in humans has also been predicted froma study on the erythemal effect of halogen lamps (17).

In any case, without renouncing to the benefits of this attractiveillumination system, the carcinogenic hazard can be easily avoided byusing common glass or suitable plastic covers that block UV radiation.In fact, all genotoxic and carcinogenic effects could be totally prevented by interposing silica glass covers between the quartz bulb andthe biological target. In some countries, glass covers are alreadycompulsory in case of mains-operated halogen lamps [ones which are

directly connected with the electric system (e.g., 110—225V) and not

through an electric transformer (e.g., 6—12V]of recent manufacturefor safety reasons due to the risk of burst consequent to the very hightemperature and internal pressure. This kind of lamp includes, amongothers, most models which are used indoor for indirect, diffuse lighting. Incidentally, UV radiation is reflected, and several experimentsindicated that the bacterial genotoxicity of uncovered halogen lampsis reduced but not eliminated by indirect lighting (18). On the other

hand, we know of no regulation for low voltage-operated halogenlamps, such as those incorporated into spotlights or desktop lamps.Recently, manufacturers of halogen lamps have introduced into themarket a new type of halogen lamp, advertised for preventing fadingof cloth, paintings, and other colored material, in which the quartzbulb is treated in such a way to block a considerable proportion of UVemissions. Genotoxicity and carcinogenicity studies are now in progress in order to check the safety of these lamps compared to traditional lamps equipped with glass covers.

Fig. 5. Time-related evolution of skin tumor multiplicityin SKH-1femalehairlessmiceexposed12,6, 3, or 1.5 h/day to the light emitted by an uncovered dichroic lamp incorporating a 12 V. 50 Whalogen quartz bulb, at an illuminance level of10,000 lux. See Table 1 for details (experiment 2).

4

2

010 15 20 25 30 35 40 45 50 55 60 65 70

Time (weeks)

5085

REFERENCES

1. Dc Flora, S., Camoirano, A., Izzotti, A., and Bennicelli, C. Potent genotoxicity ofhalogen lamps, compared to fluorescent light and sunlight. Carcinogenesis (Land.),11: 2171—2177,1990.

2. Dc Flora, S., Camoirano, A., Izzotti, A., and Bennicelli, C. A bacterial DNA repairtest evaluating the genotoxicity of light sources. Toxicol. Methods, 1: 116—122,1991.

3. D'Agostini, F., Izzotti, A., and Dc Flora, S. Induction of micronuclei in culturedhuman lymphocytes exposed to quartz halogen lamps and its prevention by glasscovers. Mutagenesis, 8: 87—90,1993.

4. Dc Flora, S., and D'Agostini, F. Halogen lamp carcinogenicity. Nature (Land.), 356:569, 1992.

5. Gallagher, C. H., Path, F. R. C., Canfield, P. J., Greenoak, G. E., and Reeve, V. E.Characterization and histogenesis of tumors in the hairless mouse produced bylow-dosage incremental ultraviolet radiation. J. Invest. Dermatol., 83: 169—174,1984.

6. Burns, F., Albert, R., Altshuler, B., and Morris, E. Approach to risk assessment forgenotoxic carcinogenesis based on data from the mouse skin initiation-promotionmodel. Environ. Health Perspect., 50: 309—320,1983.

7. Hennings, H., Shores, R., Balaschak, M., and Yuspa, S. H. Sensitivity of subpopulations of mouse skin papillomas to malignant conversion by urethane or 4-nitroquinoline N-oxide. Cancer Res., 50: 653—657,1990.

8. de Gruijl, F. R., and van der Leun, J. C. Development of skin tumors in hairless miceafter discontinuation of ultraviolet irradiation. Cancer Res., 51: 979—984,1991.

9. Cole, C. A., Davies, R. E., Forbes, P. D., and D'Aloisio, L C. Comparison of actionspectra for acute cutaneous responses to ultraviolet radiation: man and albino hairlessmouse. Photochem. Photobiol., 37: 623—631,1983.

10. International Agency for Research on Cancer. Solar and ultraviolet radiation. In:IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 55.Lyons, France: International Agency for Research on Cancer, 1992.

11. Kelfkens, G., de Gruijl, F. R., and van der Leun, J. C. Tumorigenesis by short-waveultraviolet A: papillomas versus squamous cell carcinomas. Carcinogenesis (Land.),12:1377—1382,1991.

12. de Gruijl, F. R., van der Meer, J. B., and van der Leun, J. C. Dose-time dependencyof tumour formation by chronic UV exposure. Photochem. Photobiol., 37: 53—62,1983.

13. Sterenborg, H. J. C. M., van der Putte, S. J. C., and van der Leun, J. C. Thedose-response relationship of tumorigenesis by ultraviolet radiation of 254 nanometer. Photochem. Photobiol., 47: 254—263,1988.

14. McKinlay, A. F., Whillock, M. 3., and Meulemans, C. C. E. Ultraviolet radiation andblue-light emission from spotlights incorporating tungsten halogen lamps. In: NRPBR228, pp. 1—13.Chilton, Didcot, UK: National Radiological Protection Board,1989.

15. Swerdlow, A. J., English, J. S. C., MacKie, R. M., O'Doherty, C. J., Hunter, J. A. A.,Clark, J., and Hole, D. J. fluorescent lights, ultraviolet lamps, and risk of cutaneousmelanoma. Br. Med. J., 297: 647—650,1988.

16. Elwood, J. M. Could melanoma be caused by fluorescent light? A review of relevantepidemiology. Recent Results Cancer Rca., 102: 127—136,1986.

17. Cesarini, J. P., and Muel, B. Erythema induced by quartz-halogen sources. Photodermatol. Photodermatol., 6: 222—227,1989.

18. Dc Flora, S., Camoirano, A., Izzotti, A., D'Agostini, F., and Bennicelli, C. Carcinogenic risks resulting from artificial illumination systems. Igiene Moderna, 97:818—826, 1992.

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