The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0-6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes. On multiple occasions over 6 weeks, blood high-sensitivity C-reactive protein (hs-CRP), fibrinogen, HDL- and LDL-cholesterol, and 24-h urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TxB2) were also evaluated as biomarkers of potential harm. All the biomarkers examined, except for LDL-cholesterol, discriminated with high sensitivity and specificity between adult smokers and non-smokers overall. Except for HDL-cholesterol, all biomarker medians were greater in adult smokers than in non-smokers: urine nicotine-equivalents 64.514 versus < 0.034 nmol mg-1 creatinine (p<0.001), carboxyhaemoglobin 4.0 versus 0.4% saturation (p<0.001), hs-CRP 0.27 versus 0.12 mg dl-1 (p=0.05), fibrinogen 292 versus 248 mg dl-1 (p<0.001), HDL-cholesterol 46 versus 53 mg dl-1 (p=0.003), LDL-cholesterol 119 versus 109 mg dl-1 (p=0.18), urine 8-epi-PGF2alpha 1935 versus 1034 pg mg-1 creatinine (p<0.001) and urine 11-dehydro-TxB2 973 versus 710 pg mg-1 creatinine (p<0.001). All the biomarkers of exposure and most of the biomarkers of potential harm showed no time of sampling (by visit week) effect.

AB STRACTIntracellular concentrations of cyclic AMP increase when cells are deprived of serum. Studies with the mouse fibroblast line 3T3, an SV40-transformed subline of 3T3, and six different revertant lines derived from this clone show that a marked increase in cyclic AMP occurs only when the serum concentration is reduced below the minimum necessary for growth of a given line. Conversely, density-dependent inhibition of growth is not accompanied by an increase in cyclic AMP concentration in any line.The regulation of proliferation of fibroblast cultures is complex. Well regulated cell lines, such as the mouse line 3T3, are sensitive to inhibition by at least three different environmental signals: contact with other cells (1-3), deprivation of serum (4, 5), and absence of a solid substrate (6). SV40 virus transformed 3T3 clones may lose sensitivity to all three signals, and thus grow despite cell-cell contact (2), grow even when serum is reduced by 10-fold (7), and form spherical colonies when suspended in methyl cellulose gel (8, 9) ( Table 1). This loss of growth control can be reversed. By applying negative selection pressures to transformants, we have obtained cell lines, called revertants, which exhibit growth control comparable to that of normal cells (7, 9-11). Some revertants have regained sensitivity to contact-regulations and anchorage-regulations without regaining a high serum requirement for growth. We term these "density-revertants" (10, 11) ( Table 1). Other revertants have regained a high serum requirement for growth and, in addition, sensitivity to either contact alone, or to both contact and anchorage. We term these "serum-revertants" (7) ( Table 1).Many studies have suggested a possible inhibitory role for 3': 5'-cyclic AMP (cAMP) in the regulation of proliferation of fibroblast cultures (12-19). When cAMP is measured directly in cultures of normal and transformed cell lines, the concentration of cAMP is consistently found to be about half as high in growing cultures of transformed lines (13)(14)(15)(16)(17)

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