Risk of bladder tumors among benzidine workers and their serum properdin levels.

Serum properdin levels were determined for 21 benzidine operators at 6-month intervals for 2 years after termination of exposure to this carcinogen. Of this group, 7 developed bladder cancers within a 4-month period prior to the initial assay, and all 7 showed properdin levels below the median for the group as a whole. Two of the 3 workers who had had a brief exposure previously to beta-naphthylamine developed benign bladder tumors but had no malignant neoplasms up to 13 years later. The properdin assays of these 3 men remained consistently at or above the median values. No man developed a bladder tumor who was exposed less than 6 years to benzidine, even though 2 of these men showed low properdin levels. Of the 4 whose properdin levels were initially above the median but dropped below in subsequent assays, 3 developed bladder cancers 0.5, 4, and 9 years later. Only 1 man whose properdin level remained high in 1958-59 developed a bladder cancer 7 years later, and his immunologic picture may have been complicated by recovery from a larynx tumor in 1954. Recurrence of bladder tumors among the original 9 cases has occurred only among the 5 whose properdin levels remained below the median. The 1 whose ranking fell most dramatically (from 13 to 19) has had 13 recurrences in 13 years.

Correlation of cocarcinogenic activity among n-alkanes with their physical effects on phospholipid micelles.

N-alkanes from C12 to C28 were tested for their cocarcinogenic or promoting activities to evaluate a correlation of their biologic activity with their effects on transport properties of phospholipid micelles. On this basis, we had predicted that the C18 and C20 homologues would be more active than the better known dodecane. The C12, C16, C18, and C20 n-alkanes, at various dilutions from 6 to 40% by volume in decahydronaphthalene (Decalin), were tested for their relative activity in a cocarcinogenic relationship to benzo[a]pyrene. At a 20% alkane concentration level, the solutions containing octadecane and eicosane induced tumors most rapidly. A 40% dodecane concentration was required to produce this level of cocarcinogenic activity. The activity of octadecane paralleled its physical effects on transport kinetics closely in the 6-40% (by volume) concentration. The C18, C20, and C28 n-alkanes and the C30 olefin squalene at dilutions from 10 to 40% in Decalin (by volume) were tested for their relative promoting activity after a single application of 7,12-dimethylbenz[a]anthracene in benzene. At comparable mole fractions in Decalin, the three n-alkanes had essentially the same promoting activity; squalene, at 20%, showed only borderline activity. Thus the high biologic activity of the C18, C20, and C28 n-alkanes correlated well with their physical effects on the structure of phospholipid micelles (chain-chain interactions of the alkanes with the acyl chains of the lipid). This correlation was interpreted as a strong indication that the liquid crystalline region of the phospholipid assembly (adjacent to the aqueous interface) in the membranes of latent (initiated) cancer cells was the site of action of hydrocarbon cocarcinogens. Application of a modified physical model to pristane, a branched-chain C19 alkane from coal and Colorado shale, indicated higher cocarcinogenic activity than that of n-C18H38. Applied to purified samples of docosane and tetracosane, activity comparable to that of octadecane was indicated.

Indoor tobacco smoke pollution. A major risk factor for both breast and lung cancer?

Among 51 countries, those having high mortality rates for male lung cancer generally have high rates for female breast cancer (highest in England, Scotland, and the Netherlands). Conversely, those having low rates for one disease have low rates for both (P less than 0.001). Mortality rates available for 23 of the countries for 1954, 1964, and 1974 show a constant relationship of the female breast cancer rate, y = 13.3 + 0.17x (where x is the male lung cancer rate). Where data on 1950 tobacco consumption are available (20 countries), an even closer relationship with female breast cancer mortality in 1974 is observed. Because women in many of these countries account for only a small fraction of the tobacco consumption, the conclusion is that the risk of the female disease is closely related to the extent of male smoking. Thus, breast cancer is apparently initiated by the involuntary inhalation of indoor tobacco smoke for more than two decades on the average before diagnosis. The same relationship between female breast and male lung cancer is found in incidence rates for 80 populations of five continents, including northern and western populations of the US. Trends in age-adjusted breast cancer incidence rates rose almost 50% in many of these populations from 1950 to 1975. This increase corresponds to a tripling of cigarette consumption in the US from 1927 to 1952. There is a strong need to analyze passive smoking more than two decades before diagnosis as a confounding variable in all studies of other risk factors for breast cancer such as alcohol, dietary fat, and endogenous or exogenous estrogen. Comparison of incidence rates for lung cancer and lifetime cigarette consumption in various cultures of Hawaii indicates that even for male smokers, additional exposure to high levels of indoor tobacco smoke greatly increases their risk of lung cancer. This brings the safety of designated smoking areas into serious question.

Epidemiologic evidence for the role of indoor tobacco smoke as an initiator of human breast carcinogenesis.

Earlier research suggested an appreciable latent period between the time of exposure to indoor tobacco smoke and the detection of breast cancer. A close relationship was found in the U.S. between state breast cancer mortality from 1978 through 1981 and state cigarette sales from 1950 through 1954 (R = 0.64, p less than 0.001). The correlation declined for sales in subsequent years but remained highly significant until 1970, but not thereafter. Thus, it appears that the role of indoor tobacco smoke in breast carcinogenesis is that of an initiator and/or an early-stage promoter in the process that leads after 15 to 30+ years to cancer. Trends in cigarette consumption from 1915 to 1965 paralleled breast cancer incidence in Connecticut women from 1935 to 1989. The 1953 and 1975 peaks in incidence were related to 1930 and 1953 peaks in cigarette consumption, respectively, showing a 22.5-year latent period. The drop in cigarette sales in the mid-1950s was followed by a surge to new highs in sales in the early 1960s in the great majority of the states. Approximately 23 years later, breast cancer incidence rates in the mid-1980s in all nine SEER populations are reflecting that surge in cigarette sales, rising to an all-time high in 1985. The earliest declines in breast cancer incidence should occur in New York and Connecticut, where cigarette sales have fallen most dramatically. By the year 2015, white women in the South, currently living with the men with the highest lung cancer rates in the U.S., are expected to show the highest breast cancer rates in the country.