Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter.

Results from a population-based case-control study of cancer of the renal pelvis and ureter are reported. Telephone interviews were conducted with 187 residents of Los Angeles County diagnosed with cancer of the renal pelvis and ureter over a 4-year period ending December 31, 1982, and with individually sex-, age- and race-matched neighborhood controls. The major risk factor identified for cancer of the renal pelvis and ureter was cigarette smoking. Subjects who smoked more than 25 years had a relative risk of 4.5 of developing these tumors, compared to nonsmokers (P less than 0.0001). Heavy use of over-the-counter analgesics was also associated with a significant increase in risk; it appears that an elevated risk was conveyed by all the major active constituents of those compounds currently marketed in the United States, aspirin, caffeine, and acetaminophen. Persons who had used these drugs for 30 consecutive days at any time in their life preceding diagnosis had twice the risk of developing cancer of the renal pelvis or ureter compared to persons not reporting such use (P less than 0.01). Heavy coffee drinkers (greater than or equal to 7 cups/day) had a 1.8-fold increase in risk compared to nondrinkers. Although risk tended to increase with increasing consumption, this result was not statistically significant. The risk associated with heavy coffee consumption was reduced to 1.3 after adjusting for smoking. Nine cases compared to no controls reported a first degree relative with kidney cancer. A history of kidney stones was associated with an increased risk of cancer of the ureter (relative risk = 2.5) that was not, however, statistically significant.

In vitro genotoxicity studies using complex hydrophobic mixtures: efficient delivery of a petroleum sample to cultured C3H/10T1/2 cells via lipid vesicle incorporation.

Petroleum fractions are a diverse group of extremely hydrophobic mixtures, some of which display strong carcinogenicity in animal skin painting experiments. Interpretation of in vitro genotoxicity experiments with these samples is complicated by inefficient delivery of these hydrophobic substances inside target cells. We therefore developed methods to assess and improve the efficiency of delivering a petroleum sample (Matrix, A.P.I. 81-17) to cultured C3H/10T1/2 cells for genotoxicity studies via lipid vesicle incorporation. Three radiolabeled compounds (14C-benzo(a)pyrene, 14C-decane, and 14C-naphthalene) of widely differing volatilities, broadly representative of the spectrum of compounds in petroleum samples, were separately added to Matrix. Lipid vesicles containing Matrix and radiolabeled compounds were prepared by the classical methods for preparing neutral, positive, and negatively charged multilamellar and unilamellar liposomes. Of these, the classical methods for preparing neutral unilamellar liposomes were the most successful for delivering radiolabeled compounds in Matrix to cells. Vesicles optimal for the delivery of tracers in Matrix were prepared with DSPC:cholesterol:lyso-PC (8.8:0.8:0.4, molar ratio) in a Matrix to lipid ratio of 31:69 (w/w). This new method of delivery resulted in proportional, dose-dependent, and reproducible uptake of all tracers. Further, cells treated with this preparation took up 2.5-fold more 14C-decane, 1.5-fold more 14C-BaP, and 18-fold more 14C-naphthalene added to Matrix than did cells treated with Matrix emulsified in tissue culture medium. In contrast, tracers were not taken up in a proportional or reproducible manner when emulsions were used, and in fact, uptake of 14C-naphthalene was consistently very small. Two petroleum fractions, C(2)029188 and C(3)029194, were 4- and 6-fold more cytotoxic, respectively, when delivered to C3H/10T1/2 cells by lipid vesicles than emulsions. The carcinogenic petroleum fraction C(5)0292202 induces type II transformed foci in C3H/10T1/2 cells when cells were treated with C(5)0292202 incorporated into lipid vesicles. The methods for lipid vesicle incorporation described here are effective in delivering hydrophobic petroleum fractions to cells and provide an alternative to the current inefficient and artifactual methods of emulsification currently used. With further validation and standardization, lipid vesicle incorporation of petroleum fractions and treatment of cells with these vesicles should be useful for studying the genotoxicity of complex hydrophobic mixtures in cell culture systems.