Photocarcinogenesis measuring the reproducibility of a biologic response to ultraviolet radiation exposure in mice

Abstract

New drugs undergo safety evaluations of many types. For some drugs, a photocarcinogenesis study forms one of the elements in the overall toxicology package. Photocarcinogenesis studies are designed to evaluate a drug's ability to modify the growth and development of ultraviolet radiation (UVR)-induced skin tumors in albino hairless mice. "Exposure control" groups in such studies receive the UVR, either alone, or in combination with the "vehicle" or carrier associated with each study. This report presents skin tumor data from control groups compiled from nine consecutive studies conducted at this testing facility. The endpoints evaluated included median tumor onset, mortality-free prevalence and tumor yield. "Historical control data" are considered essential for designing, monitoring, interpreting and evaluating studies of a given type. In addition, a compilation of such control data can illustrate trends or provide measures of reproducibility more reliably than can individual studies. This data set shows how clearly the UVR-induced skin tumor onset time is dependent on UVR dose, how skin tumors develop sooner in female mice than in male mice at a low UVR exposure dose, and that topical administration of certain vehicle formulations can enhance photocarcinogenesis.

Effects of an Ultraviolet B Radiation Absorber on Photocarcinogenesis in Hairless Albino Mice

“…The latency periods of 21 and 22 weeks in male and female UVR controls and 20 and 21 weeks for the UVR vehicle groups are similar to those reported by others. Sambuco et al [18] reported, for a group exposed to 1,200 RBU (RobertsonBerger units), T 50 values of approximately 25 and 24 weeks for males and females, respectively. Ananthaswamy [14] reported a T 50 value of 25 weeks for female C3H mice [20] and a T 50 value of 20 weeks when exposed to 2.7 MED/week.…”

“…The absence of a vehicle effect on photocarcinogenesis is not simply a matter of course [18] . Sambuco et al [18] reported vehicle-enhanced skin tumor development in 3 out of 8 photocarcinogenicity studies, both in male and female albino hairless mice.…”

“…The absence of a vehicle effect on photocarcinogenesis is not simply a matter of course [18] . Sambuco et al [18] reported vehicle-enhanced skin tumor development in 3 out of 8 photocarcinogenicity studies, both in male and female albino hairless mice. The latency periods of 21 and 22 weeks in male and female UVR controls and 20 and 21 weeks for the UVR vehicle groups are similar to those reported by others.…”

“…The US Food and Drug Administration (FDA), however, suggests testing chemicals which absorb UV light for phototoxicity or photocarcinogenicity [16] . Therefore, the ability of Uvinul T 150 to reduce UVR carcinogenesis was investigated in a standard FDA-type photocarcinogenesis test using albino hairless mice [17][18][19] . Vehicle .…”

Solar and ultraviolet radiation

“…Methods for testing photocarcinogenicity have been standardized to meet the requirements of regulatory agencies Sambuco et al, 2003).…”