Effects of catechol on the induction of tumors in mouse skin by 7,8-dihydroxy-7,8-dihydrobenzo[a] pyrenes

Abstract

Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and enantiomeric 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes (BaP-7,8-diols) in mouse skin. Similar to enhancement of BaP carcinogenesis, repeated concurrent applications of catechol and (+/-)-BaP-7,8-diol to mouse skin strongly enhanced (+/-)-BaP-7,8-diol tumor multiplicity and tumor incidence, and decreased latency. Co-application of catechol with the racemic or either of the enantiomers of BaP-7,8-diol in a two-stage initiation--promotion protocol increased the tumor initiating activity of racemic BaP-7,8-diol, similar to that of BaP, by approximately 50%, but had no statistically significant effect on the tumor initiating activity of the (+)- or (-)-enantiomers in mouse skin. Thus, catechol is as potent a co-carcinogen with (+/-)-BaP-7,8-diol as it is with BaP. However, as tested here catechol is a weak co-initiator when applied with (+/-)-BaP-7,8-diol or BaP.

Lung carcinogenesis by tobacco smoke

“…Phenol and catechol, major constituents of these fractions, do not possess significant tumor promoting activity when tested on mouse skin. However, catechol is a potent co‐carcinogen with the classic PAH carcinogen benzo[ a ]pyrene (BaP) as well as its proximate carcinogen BaP‐7,8‐diol, when tested on mouse skin, and fractions of cigarette smoke condensate enriched in catechol show similar activity 49–51. Co‐treatment of catechol with either BaP or BaP‐7,8‐diol produced larger tumors and caused more inflammatory changes than in the groups not treated with catechol.…”

“…Co‐treatment of catechol with either BaP or BaP‐7,8‐diol produced larger tumors and caused more inflammatory changes than in the groups not treated with catechol. The multiplicity of BaP‐7,8‐diol‐induced tumors on mouse skin was increased 14‐fold by catechol 51. Cellulose and chlorogenic acid in tobacco are good precursors to catechol in cigarette smoke 52.…”

Amended Final Report On the Safety Assessment of Pyrocatechol

“…Pyrocatechol increased the number of skin tumors per mouse by 55% at a dose of 250 jig and by 80% at a dose of 500 Ag. No significant effects were observed in the groups tested Pyrocatechol and either (+)BaP-7,8-diol or (-)BaP-7,8-diol (Melikian et al, 1989).…”

“…At a doses of 85 gg, Pyroc~.techol increased tumor multiplicity initiated by (±)BaP-7,8-iol (1 g) by 50% but had no effect on initiation by (+) or No significant effects were observed with 42.5 Ag Pyrocatechol (Melikian et al, 1989).…”

“…A number of dermal and feeding studies have been published since this review, indicating that Pyrocatechol is a cocarcinogen when administered with a variety of other carcinogens (Hasagawa et al, 1990;Hirose et al, 1987Hirose et al, , 1988Hirose et al, , 1990bHirose et al, , 1993Kurata et al, 1990;LaVoie et al, 1985;Melikian et al, 1989;Mirvish et al, 1985;Nakamura et al, 1991;Van Duuren et al, 1986;Yamaguchi et al, 1989).…”