Cancer is a disease that begins with mutation of critical genes: oncogenes and tumor suppressor genes. Our research on carcinogenic aromatic hydrocarbons indicates that depurinating hydrocarbon-DNA adducts generate oncogenic mutations found in mouse skin papillomas (Proc. Natl. Acad. Sci. USA 92:10422, 1995). These mutations arise by mis-replication of unrepaired apurinic sites derived from the loss of depurinating adducts. This relationship led us to postulate that oxidation of the carcinogenic 4-hydroxy catechol estrogens (CE) of estrone (E 1 ) and estradiol (E 2 ) to catechol estrogen-3,4-quinones (CE-3, 4-Q) results in electrophilic intermediates that covalently bind to DNA to form depurinating adducts. The resultant apurinic sites in critical genes can generate mutations that may initiate various human cancers. The noncarcinogenic 2-hydroxy CE are oxidized to CE-2,3-Q and form only stable DNA adducts. As reported here, the CE-3,4-Q were bound to DNA in vitro to form the depurinating adduct 4-OHE 1 (E 2 )-1(␣,␤)-N7Gua at 59-213 mol͞mol DNA-phosphate whereas the level of stable adducts was 0.1 mol͞mol DNA-phosphate. In female Sprague-Dawley rats treated by intramammillary injection of E 2 -3,4-Q (200 nmol) at four mammary glands, the mammary tissue contained 2.3 mol 4-OHE 2 -1(␣,␤)-N7Gua͞molDNA-phosphate. When 4-OHE 1 (E 2 ) were activated by horseradish peroxidase, lactoperoxidase, or cytochrome P450, 87-440 mol of 4-OHE 1 (E 2 )-1(␣, ␤)-N7Gua was formed. After treatment with 4-OHE 2 , rat mammary tissue contained 1.4 mol of adduct͞mol DNA-phosphate. In each case, the level of stable adducts was negligible. These results, complemented by other data, strongly support the hypothesis that CE-3,4-Q are endogenous tumor initiators.

Eighty‐two periodontal patients were treated in a split mouth design with coronal scaling (CS), root planing (RP), modified Widman surgery (MW), and flap with osseous resection surgery (FO) which were randomly assigned to various quadrants in the dentition. Therapy was performed in 3 phases: non‐surgical, surgical, and supportive periodontal treatment (SPT) ≤ 7 years. Clinical data consisted of probing depth (PD), clinical attachment level (CAL), gingival recession (REC), bleeding on probing (BOP), suppuration (SUP), and supragingival plaque (PL). Because of the necessity to exit many CS treated sites due to breakdown, data for CS were reported only up to 2 years. All therapies produced mean PD reduction with FO > MW > RP > CS following the surgical phase for all probing depth severities. By the end of year 2 there were no differences between the therapies in the 1 to 4 mm sites. There were no differences in PD reduction between MW and RP treated sites by the end of year 3 in the 5 to 6 mm sites and by the end of year 5 in the ≥ 7 mm sites. FO produced greater PD reduction in ≥ 5 mm sites through year 7 of SPT. Following the surgical phase, FO produced a mean CAL loss and CS and RP produced a slight gain in 1–4 mm sites. RP and MW produced a greater gain of CAL than CS and FO following the surgical phase in 5 to 6 mm sites, but the magnitude of difference decreased during SPT. Similar CAL gains were produced by RP, MW, and FO in sites ≥ 7 mm. These gains were greater than that produced by CS and were sustained during SPT. Recession was produced with FO > MW > RP > CS. This relationship was maintained throughout SPT. The prevalences of BOP, SUP, and PL were greatly reduced throughout the study and were comparable between sites treated by RP, MW, and FO while the CS sites had more BOP and SUP. J Periodontol 1996;67:93–102.

Seventy-four patients with moderate to advanced periodontitis were classified by cigarette consumption at the initial exam: heavy smokers (HS) > or = 20 cigarettes/day (n = 31); light smokers (LS) < or = 19 cigarettes/day (n = 15); past smokers (PS) had a history of smoking but had quit by the initial exam (n = 10); and non-smokers (NS) had never smoked (n = 18). All patients were treated with four modalities of periodontal therapy followed by supportive periodontal treatment (SPT) for a period of up to 7 years. Clinical parameters including probing depth (PD), clinical attachment level (CAL), recession (REC), presence of bleeding on probing (BOP), and supragingival plaque (PL) were assessed at six sites around each tooth. Horizontal probing attachment level (HAL) was obtained at molar furcation sites. Data were collected initially, 4 weeks after non-surgical therapy, 10 weeks after surgical therapy, and yearly during SPT. HS and LS demonstrated less PD reduction and less CAL gain than PS and NS following active treatment and throughout SPT. Following active treatment, HAL changes were similar for all groups, but during 7 years of SPT, HS and LS experienced greater loss of HAL. There were no differences in BOP among the four groups. HS demonstrated a higher percentage of PL positive sites compared to the other groups. In summary, HS and LS responded less favorably to therapy than PS and NS. A past history of smoking was not deleterious to the response to therapy.

The purpose of this 2-year longitudinal clinical study was to investigate alveolar (oral) bone height and density changes in osteoporotic/osteopenic women compared with women with normal lumbar spine bone mineral density (BMD). Thirty-eight postmenopausal women completed this study; 21 women had normal BMD of the lumbar spine, while 17 women had osteoporosis or osteopenia of the lumbar spine at baseline. All subjects had a history of periodontitis and participated in 3- to 4-month periodontal maintenance programs. No subjects were current smokers. All patients were within 5 years of menopause at the start of the study. Four vertical bitewing radiographs of posterior sextants were taken at baseline and 2-year visits. Radiographs were examined using computer-assisted densitometric image analysis (CADIA) for changes in bone density at the crestal and subcrestal regions of interproximal bone. Changes in alveolar bone height were also measured. Radiographic data were analyzed by the t-test for two independent samples. Osteoporotic/osteopenic women exhibited a higher frequency of alveolar bone height loss (p<0.05) and crestal (p<0.025) and subcrestal (p<0.03) density loss relative to women with normal BMD. Estrogen deficiency was associated with increased frequency of alveolar bone crestal density loss in the osteoporotic/osteopenic women and in the overall study population (p<0.05). These data suggest that osteoporosis/osteopenia and estrogen deficiency are risk factors for alveolar bone density loss in postmenopausal women with a history of periodontitis.