INCREASED FREQUENCY OF RESISTANCE TO TERMINAL DIFFERENTIATION IN C3H MOUSE CELLS PRODUCED BY GENOTOXIC BUT NOT NONGENOTOXIC CARCINOGENS

Certain cells present in mouse skin are resistant to calcium-induced t erminal differentiation. It is believed that these calcium-resistant c ells (CRCs) represent an early stage in the carcinogenic process, in p art, because frequency increases after treatment with mutagens. The fr equency of CRCs in C3H mouse skin was measured before and after treatm ent with certain petroleum-derived materials. One objective was to det ermine whether this assay could differentiate between genotoxic and no ngenotoxic mouse skin carcinogens. An additional objective was to dete rmine whether CRCs are an important factor in the tumorigenicity of pe troleum middle distillates (PMDs), a class of apparently nongenotoxic materials. Three petroleum-derived materials were tested: mineral oil (MO), a noncarcinogenic product used as the negative control; catalyti cally cracked clarified oil (CCCO), a highly carcinogenic and mutageni c material; and a lightly refined paraffinic oil (LRPO), a PMD which h as produced tumors when repeatedly applied, but is not mutagenic and d oes not initiate mouse skin tumors. The CRC frequency was not increase d by LRPO treatment; however, a statistically significant and dose-rel ated increase was produced by CCCO. These results are consistent with observations that genotoxic, petroleum-derived liquids are capable of tumor initiation in mouse skin, whereas PMDs which are not genotoxic d o not initiate skin tumors. The number of CRCs in untreated and MO-tre ated mice was approximately twice the tumor frequency measured in bioa ssays of PMDs. Thus, tumor production associated with these products c ould be due to promotion of preexisting, spontaneously initiated cells . (C) 1994 Society of Toxicology.